F.H. Rola

Peripheral neuropathy and neurological disorders in an unselected Brazilian population-based cohort of IBD patients.

Background: Several neurological disorders have been described in inflammatory bowel disease (IBD) patients, but their exact frequency is unknown. Methods: We prospectively studied the prevalence of neurological disorders (especially peripheral neuropathy) in a group of 82 patients with Crohns disease (CD, n = 31) or ulcerative colitis (UC, n = 51) from 2 Brazilian tertiary care university clinics and followed them through a period of at least 1 year. All patients were interviewed and had complete neurological evaluations. Results: Large‐fiber sensory or sensorimotor polyneuropathy (PN) was observed in 16.1% of the CD and 19.6% of the UC patients. PN was usually mild, predominantly symmetric, and distal with axonal involvement. One patient had demyelinating PN at the diagnosis of CD. Mild carpal tunnel syndrome was common in female UC patients. Sensory symptoms without electromyography abnormalities, suggestive of small‐fiber neuropathy or subclinical myelopathy, affected 29% and 11.8%, respectively. After excluding other known etiological or contributory factors for PN, 13.4% of the IBD patients had otherwise unexplained large‐fiber or small‐fiber PN (7.3% with large‐fiber SM PN). Nondebilitating headache was the most common neurological complaint. Three patients had ischemic strokes, 5 were epileptic, and 1 transient chorea. Conclusions: Neurological disorders, especially PN, are common in our Brazilian cohort of IBD patients. They are diverse, multifactorial, and more common in women. Despite the mild phenotype in most cases, attention should be given by the general practitioner and gastroenterologist since they are frequently undiagnosed. Further studies are necessary to confirm these findings in populations with different genetic and nutritional backgrounds.

Sildenafil, a phosphodiesterase-5 inhibitor, delays gastric emptying and gastrointestinal transit of liquid in awake rats.

We studied the effect of sildenafil on gastric emptying (GE) and gastrointestinal (GI) transit in awake rats. After cervical vessel cannulation and 24 hr of fasting, the animals received an intravenous (IV) injection of sildenafil (4 mg/kg) or vehicle. Next they were gavage fed (1.5 ml) with a test meal (phenol red in 5% glucose solution, 0.5 mg/ml) and sacrificed 10, 20, or 30 min later. Experimental and control subsets consisted of 5–10 rats. Gastric and proximal, medial, and distal small intestine dye retentions (GDR and IDR, respectively) were obtained by spectrophotometry. Data were compared by ANOVA and Student-Newman-Keuls test. In sildenafil-treated animals, GDR increased (P < 0.05) by 20.3%, 46.9%, and 55,5% while medial IDR decreased (P < 0.05) by 35.1%, 43.4%, and 41.6%, respectively, at 10, 20, and 30-min intervals. Proximal and distal IDR values did not change in sildenafil-treated animals. Mean arterial pressure (MAP) decreased 25% (P < 0.05) right after sildenafil administration but normalized afterwards while in controls MAP remained unchanged. In conclusion, sildenafil delays GE and GI transit of a liquid meal while transiently decreases MAP in awake rats.

Complete cervical or thoracic spinal cord transections delay gastric emptying and gastrointestinal transit of liquid in awake rats

Study Design: To determine the changes on gastric emptying and gastrointestinal transit of liquid throughout the first week after spinal cord transection (SCT) in rats. Methods: Male Wistar rats (n=121) were fasted for 16 h and a complete SCT or laminectomy was performed between C7 and T1 (cervical group) or between T4 and T5 (thoracic group). Dye recovery in the stomach, proximal, mid and distal small intestine was determined 30 min, 6 h, 1, 3 or 7 days after surgery. The test meal (1.5 ml of a phenol red solution, 0.5 mg/ml in 5% glucose) was intragastrically administered and the animals sacrificed by cervical dislocation 10 min later. Results: Cervical SCT increased dye recovery in the stomach (P<0.05) by 70.1, 78.7, 34.2, 41.3 and 50.9% while it decreased recovery in the mid small intestine (P<0.05) by 87.1, 85.1, 74.8, 59.5 and 80.1%, respectively 30 min, 6 h, 1, 3 and 7 days after SCT. Thoracic SCT increased gastric recovery (P<0.05) by 43.5, 67.6, 51.2, 75.4 and 38.9% while it decreased recovery in the mid small intestine (P<0.05) by 100, 100, 45.6, 100 and 66.6%, respectively 30 min, 6 h, 1, 3 and 7 days after SCT. A separate group was submitted to laminectomy+bilateral sciatic nerve transection (paraplegic sham). Gastric emptying and gastrointestinal transit were not inhibited in this group. Conclusion: In summary, gastric emptying and gastrointestinal transit of liquid are inhibited throughout the first week after high SCT in awake rats.

Evaluation of gastrointestinal motility in awake rats: a learning exercise for undergraduate biomedical students

Current medical curricula devote scarce time for practical activities on digestive physiology, despite frequent misconceptions about dyspepsia and dysmotility phenomena. Thus, we designed a hands-on activity followed by a small-group discussion on gut motility. Male awake rats were randomly submitted to insulin, control, or hypertonic protocols. Insulin and control rats were gavage fed with 5% glucose solution, whereas hypertonic-fed rats were gavage fed with 50% glucose solution. Insulin treatment was performed 30 min before a meal. All meals (1.5 ml) contained an equal mass of phenol red dye. After 10, 15, or 20 min of meal gavage, rats were euthanized. Each subset consisted of six to eight rats. Dye recovery in the stomach and proximal, middle, and distal small intestine was measured by spectrophotometry, a safe and reliable method that can be performed by minimally trained students. In a separate group of rats, we used the same protocols except that the test meal contained (99m)Tc as a marker. Compared with control, the hypertonic meal delayed gastric emptying and gastrointestinal transit, whereas insulinic hypoglycemia accelerated them. The session helped engage our undergraduate students in observing and analyzing gut motor behavior. In conclusion, the fractional dye retention test can be used as a teaching tool to strengthen the understanding of basic physiopathological features of gastrointestinal motility.

Heart rate analysis differentiates dialeptic complex partial temporal lobe seizures from auras and non-epileptic seizures

The distinction of non-epileptic from epileptic events is difficult even for experienced neurologists. We retrospectively evaluated 59 dialeptic events from 27 patients admitted for video EEG monitoring to check whether heart rate (HR) analysis could help in differentiating dialeptic complex partial temporal lobe seizures (TLS) from dialeptic simple partial TLS, and non-epileptic dialeptic events. Baseline HR was increased in the simple partial TLS in comparison to complex partial TLS and non-epileptic groups (p<0.05). HR increase accompanied each individual dialeptic complex partial TLS (100% of the events, p<0.05) bur HR returned to baseline in the post-ictal phase. Ictal HR was not altered in the non-epileptic or simple partial TLS groups. Our findings suggest that ictal centrally mediated tachycardia is characteristic of dialeptic TLS (both tachycardia and bradycardia have been reported during TLS). This finding may be used as a criterion to distinguish dialeptic complex partial TLS from simple partial and non-epileptic dialeptic events.

Gastric Emptying and Gastrointestinal Transit of Liquid Throughout the First Month After Thoracic Spinal Cord Transection in Awake Rats

Spinal cord transection (SCT) inhibits gastrointestinal motility in awake rats. We studied the gastric emptying (GE) and gastrointestinal transit of liquid throughout the first month after thoracic SCT. Male Wistar rats (N = 66) were submitted to laminectomy followed or not by complete SCT between T4 and T5 vertebrae. Phenol red recovery in the stomach, proximal, mid-and distal small intestine was determined 1, 7, 10, 15, and 30 days thereafter. Gastric recovery increased by 51.2 and 38.9% and mid-intestinal recovery decreased by 45.5 and 66.6% at one and seven days after SCT (P < 0.05). Proximal small intestine recovery increased by 45.9% 10 days after SCT but no inhibition of gastrointestinal motility was observed thereafter. Stool output significantly decreased in the first seven days after SCT (P < 0.05). In summary, gastrointestinal motility in awake rats is inhibited throughout the first 10 days after thoracic SCT but not thereafter.

Effect of preinjury large bowel emptying on the inhibition of upper gastrointestinal motility after spinal cord injury in rats.

Spinal cord transection (SCT) inhibits gastrointestinal motility in rats. We evaluated the effect of preinjury large bowel emptying on this phenomenon. Male Wistar rats (N = 52) were fasted for 24 or 48 hr with water ad libitum and pretreated with lactose (0.8 g) or saline. Next, laminectomy followed or not by complete SCT between T4 and T5 vertebrae was performed. Phenol red recovery in the stomach and proximal, medial, and distal small intestine was determined 1 day later. In animals submitted to 24 hr fasting + saline, SCT increased gastric recovery by 42.8% decreased medial small intestine recovery by 56.2%, while 48 hr fasting + saline or 24 hr fasting + lactose prevented the inhibition of gastric emptying (GE) in SCT animals. The 48 hr fasting + lactose prevented the inhibition of both GE and gastrointestinal transit. SCT-induced inhibition of upper gastrointestinal motility may involve enhancement of inhibitory reflexes, which can be prevented by large bowel emptying.

Acute hypervolaemia increases gastroduodenal resistance to the flow of liquid in the rat.

The effect of volume expansion of extracellular fluid on gastroduodenal resistance to the flow of isotonic saline was assessed in three groups of rats using intravenous infusions of isotonic, isotonic-isoncotic, and isotonic-isoncotic-isohaemic solutions. The gastroduodenal segment of 29 male Wistar rats was barostatically perfused at a constant pressure gradient of 4 cm H2O and changes in flow (ml/minute) were taken as a reflection of changes in gastroduodenal resistance. Isotonic expansion led to a 33% drop in gastroduodenal flow compared with the normovolaemic period in the same animals (p less than 0.01). Extracellular fluid expansion with isotonic-isoncotic and isotonic-isoncotic-isohaemic solutions was associated with reductions in gastroduodenal flow of 29% (p less than 0.05) and 31% (p less than 0.01) respectively. The increase in gastroduodenal resistance is due to hypervolaemia per se and not to haemodilution, decreases in plasma oncotic pressure, or electrolyte imbalance. The effect of hypervolaemia on gastroduodenal resistance, which was reversed by small haemorrhages (0.5-1.0 ml per 100 g body weight), may be due to changes in tonus or phasic motor activity, or both, and may be part of the homeostatic processes that help the organism minimise liquid volume excess.

Clinical and Electrodiagnostic Findings in Patients with Peripheral Neuropathy and Inflammatory Bowel Disease.

Background:Several neurological diseases, especially different types of peripheral neuropathy (PN) are common in inflammatory bowel disease (IBD). Methods:We prospectively evaluated the presence of PN in 121 patients with IBD (51 with Crohns disease [CD] and 70 with ulcerative colitis [UC]) and 50 controls (gastritis and dyspepsia) over 3.5 years. Results:A total of 15 patients (12.4%) with small-fiber neuropathy and IBD (7 CD and 8 UC) and 24 patients (19.8%) with large-fiber PN (12 CD and 12 UC) were diagnosed. Small-fiber neuropathy affected 6% and large-fiber PN affected 4% of the control patients. Patients with CD with PN were older, had more metabolic complications and more severe motor involvement than patients with UC with PN. Carpal tunnel syndrome was more common in patients with UC. Sural and median sensory nerves were the most commonly and severely affected sensory responses. Tibial, peroneal, median, and ulnar compound muscle action potential amplitudes were also significantly decreased in patients with CD and UC. In general, sensory and motor amplitudes were a more sensitive marker for PN in patients with IBD than conduction velocities. Conclusions:In summary, PN is common in patients with IBD. It may be primarily related to IBD, phenotypically modified by metabolic complications. Its phenotype is diverse (most commonly small to predominantly axonal sensory large-fiber), but usually more severe in CD. It also includes ataxic and demyelinating forms. Results from our 10-year follow-up will elucidate the PN clinical course and the real impact of the comorbidities and new therapies.

A plethysmometric method for gastric compliance studies in anesthetized rats

A new method to study gastric volume by plethysmography is presented. Twenty male Wistar rats (250-300 g) were fasted for 24 h. After anesthesia with urethane (1.2 g/kg, i.p.), a tracheostomy was performed, and cervical vessels were cannulated. A balloon catheter was introduced per os and positioned in the proximal stomach. The opposite end of the catheter was connected to a reservoir (volume = 30 ml; inside diameter = 2.5 cm), coupled to a plethysmometer. A standard ionic solution was used to fill the balloon ( approximately 3.0 ml) and the communicating vessel system. Calibration experiments (n = 5) displayed a strong (r(2) = 0.99) correlation between graded balloon-volume changes and plethysmometric recordings. Because distending pressure of the stomach remained constant, the balloon-volume recordings were taken as gastric compliance index. Gastric volume changes, mean arterial pressure, and heart rate of animals of control and experimental groups were monitored for 90 min. The data were analyzed by analysis of variance and the Student-Newman-Keuls test. In control animals (n = 5), no significant changes on gastric volume and hemodynamic values were found. Experimental animals were treated with either yohimbine (n = 5) or bethanechol (n = 5) i.v. injections. The rats received consecutive doses of yohimbine (0.5 and 1 mg/kg) or bethanechol (1.5 and 3 microg/kg), 30 min apart. Both doses of each treatment transiently induced hypotension and bradycardia (p < 0.05). Yohimbine treatment (1 mg/kg) increased gastric volume by half (p < 0.05), whereas bethanechol (3 microg/kg) decreased it by 35% (p < 0.05). In summary, this work shows a suitable method to directly assess gastric compliance in anesthetized rats.