Syndromic craniosynostosis is most commonly associated with mutations in Fibroblast Growth Factor Receptor genes (FGFR)-1, 2 and 3. Clinical and animal reports suggest a link between FGFR-associated craniosynostosis and defects in the gastrointestinal tract (GIT). Objective: to determine whether GIT malformations occur more frequently in the craniosynostosis population with a known FGFR mutation when compared to the general population. Methods: A retrospective chart review of patients diagnosed with Crouzon, Pfeiffer or Apert syndromes between 1990 and 2011 was performed at the Hospital for Sick Children in Toronto. Thirty-two charts meeting inclusion criteria were analyzed for any history of GIT abnormalities. Results: Three out of 32 patients had documented intestinal/bowel malrotations while 7 had gastroesophageal reflux disease. All patients had documented FGFR2 mutations, a finding in line with previous studies and published case reports. Conclusions: Results suggest an association between FGFR-associated craniosynostosis and GIT malformations.

BACKGROUND: Non malignant invasive tumors of the colon and rectum are very rare. Gastrointestinal Basidiobolomycosis can present as a mass lesion mimicking colorectal cancer. CASE PRESENTATION: A 56 year old Caucasian male was evaluated for abdominal and pelvic pain for 4 weeks complicated by acute urinary retention. Radiological evaluation showed him to have recto-sigmoid and cecal mass. Endoscopic examination and biopsies did not reveal a definite diagnosis. Computerized tomography guided biopsy of the mass showed fungal elements consistent with gastrointestinal basidiobolomycosis. He was treated with Itraconazole for 12 months with very good clinical and radiological response. CONCLUSION: Basidiobolomycosis of the gastrointestinal tract should be considered during evaluation of colorectal masses with atypical presentation. It is a rare entity seen more in endemic regions of the world for basidiobolomycosis including southwestern United States.

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Surgery / Doctoral / Doctor of Philosophy

Several feeding-related factors can affect taste sensitivity or preferences and therefore may be part of a homeostatic regulatory mechanism. Cholecystokinin (CCK), a hormone which reduces food intake in several species, has also been postulated to interact with the orosensory characteristics of food. To test this hypothesis, the effects of CCK-8 and food deprivation on the short-term intakes of water, sucrose solutions (0.05 to 1.0 M), and saline solutions (0.05 and 0.15 M) were determined. In most cases, CCK (2 μg/kg) reduced sucrose intake when measured either as the amount consumed or the number of licks in a short period (nine minutes). Additionally, CCK reduced the intake of 0.15 M NaCl in satiated rats and water intake in both hungry and satiated rats. Rats usually consumed more sucrose when hungry than when satiated or fed ad libitum; CCK-induced suppression of intake, however, was generally greater in the satiated or ad libitum conditions than in the hungry condition. There was no systematic effect of sucrose concentration on the amount of CCK-induced suppression of intake, which suggests that CCK regulates rather than interferes with ingestion. To determine whether the CCK-induced suppression is due to a change in the peripheral taste signal, the integrated chorda tympani responses to sucrose and NaCl tastes were recorded in rats anesthetized with either urethane, Innovar-Vet, or a combination of urethane and alpha-chloralose. The only significant effect of CCK was the slight increase in the initial response to 0.3 M sucrose after the infusion of a total of 10 μg of CCK-8 into rats anesthetized with Innovar-Vet. In general, therefore, the effect of CCK on sucrose intake does not appear to be due to a peripheral taste change; an analysis of single taste fibers, however, would be more conclusive. An examination of the effects of CCK on central gustatory and reward areas might yet provide a mechanism for the CCK effect on taste-motivated ingestion.

The complex interaction between the central nervous system, the enteric nervous system and local and endocrine hormones enables drugs affecting gastrointestinal motility to produce their effects through multiple sites and mechanisms of action. Opiates are one class of drugs which can have dramatic effects on gastrointestinal function and the mechanisms for these actions have been the subject of intense study in recent years. These changes in motility have assumed increased importance following the discovery of several endogenous opioid peptides. In the present studies, centrally-administered morphine was more potent than peripherally-administered morphine at inhibiting intestinal propulsion and gastric emptying in rats. Direct measurement of intestinal motility revealed that the antipropulsive effects of morphine were due to an inhibition of intestinal contractions. The opioid peptide, β-endorphin, and a stabilized enkephalin analog, [D-Ala², Met⁵] enkephalinamide, also inhibited intestinal propulsion only after central administration. These effects were not blocked by a peripherally selective opioid receptor antagonist, diallylnormorphinium. These data indicated that there is an opioid sensitive mechanism in the brain of rats that, when activated, can inhibit intestinal motility. Physiological activation, by electroconvulsive shock or inescapable footshock, or pharamcological activation by kyotorphin (Tyr-Arg) treatment, did not affect gastrointestinal motility but did produce naloxone-reversible analgesia. These data indicate that the opioid mechanisms mediating analgesia and inhibition of intestinal motility are independent and may be a function of different receptor systems. Several opioid receptor selective agonists were used to determine the specific receptors mediating the analgesic and motility effects of centrally-administered opioids. Mu selective agonists produced analgesia and inhibition of intestinal transit, while delta receptor agonists produced analgesia only. Kappa agonists did not produce analgesia or an inhibition of intestinal motility. Mu receptors mediate the analgesic and intestinal motility effects of exogenously administered opioids, while delta receptors can mediate analgesia without altering gut motility. It appears then, that electroconvulsive shock, inescapable footshock and kyotorphin may produce their analgesic effects by releasing enkephalins, which are delta selective agonists. This accounts for the failure of these treatments to alter gastrointestinal motility while still producing the analgesic effects reported here.

Motility of the small intestine is a result of complex neurochemical and hormonal interactions within the intestine. The net motility (contraction) of the intestine is a balance of the influences from the central nervous system, enteric nervous system and hormonal changes in the body. Recently, the discovery of several peptide neurotransmitters common to the brain and the intestine has stimulated new research into the influence of these novel neurotransmitter candidates on intestinal motility at the level of the enteric (intestinal) nervous system. The present studies examined the contractile actions of three families of peptides, the opioids, tachykinins and motilin. Each of these peptide groups has been localized in the intestine, and suggested to function in the control of intestinal motility. The peptides were administered by intraarterial injection to isolated segments of canine small intestine and the resulting contractile activity measured. The results of these experiments demonstrate that all of these peptides may elicit contractile activity of the intestine in very low doses. These actions were further examined, using pharmacological antagonists, to determine the mechanism of action and the receptor types involved in the contractile actions. The opioid peptide induced responses were found to be mediated by two receptor types, mu and delta, located on the enteric nerve and smooth muscle, respectively. Similarly, the tachykinin induced contractions were also found to be due to actions on two receptor types, SP-P and SP-K, located on the nerve and muscle layers, respectively. These data suggest that the opioids and tachykinins may have multiple functions in the intestine dependent on the site of action and the receptor type involved in the response. Administration of motilin induced long-lasting contractile patterns in the intestine. The results also suggest that the actions of motilin are mediated by intermediate neurons of the enteric plexes which synapse on terminal cholinergic motor neurons.

No description available.

No description available.

The purpose of this investigation was to determine the effect of solute carbonation and carbohydrate (CHO) concentration on gastric emptying during prolonged cycling. Eight highly trained male cyclists completed four two hour cycling bouts during which one of four test solutions were consumed. The test solutions consisted of a carbonated 10 % CHO solution (CK), a non-carbonated 10 % CHO solution (NCK), a carbonated non-CHO solution (CNK), and a noncarbonated non-CHO solution (NCNK). Approximately 150 ml (8.5 ml/kg/hr) of one of the test solutions were consumed every fifteen minutes. The first 105 minutes of each trial was a continuous ride on an electrically braked cycle ergometer at 70 % V02 max. The last fifteen minutes of each trial was a self paced "performance ride" on an isokinetic cycle ergometer. The subjects were instructed to complete as much work (kilojuoles) as possible during the performance ride. Gastric contents were aspirated within five minutes following the performance ride and analyzed to determine the amount of the original test solution emptied.Of the original1273 ml ingested during each trial, the volumes emptied were 993.6 ±78.1, 1064.6 ±75.3, 1097.4 ±94.2, and 1147.2 ±95.9 ml (±SE) for CK, NCK, CNK, NCNK, respectively. The only significant difference was between trials CK and NCNK (P < 0.05). There were no statistically significant differences in total work output between any of the trials. However, when the performance data from the CHO trials were pooled and compared to the combined data from the non-CHO trials, total work output was significantly greater (P < 0.05) in the CHO group (1185.19 + 21.81, and 1092.85 + 21.52 Kj (+ SE) for the CHO and non-CHO groups, respectively). These data suggest that carbonated or 10 % CHO solutions, independent of one another, may not significantly inhibit gastric emptying. They also suggest that there may be some interaction between carbonation and CHO concentration which caused an additional inhibition of emptying. In addition, the potential for improved performance exists with the consumption of 10 % CHO solutions. / Human Performance Laboratory