Taisuke Nomura

Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome

Background—Corticotropin-releasing hormone (CRH) plays a key role in modulating intestinal motility in stressed animals. Aims—To evaluate the effect of CRH on intestinal motility in humans and to determine whether patients with irritable bowel syndrome (IBS) have an exaggerated response to CRH. Subjects—Ten IBS patients diagnosed by Rome criteria and 10 healthy controls. Methods—CRH (2 μg/kg) was intravenously administered during duodenal and colonic manometry and plasma adrenocorticotropic hormone (ACTH) was measured by radioimmunoassay. Results—CRH induced motility of the descending colon in both groups (p<0.001) and induced greater motility indexes in IBS patients than in controls (p<0.05). CRH produced duodenal phase III motor activity in 80% of the subjects and duodenal dysmotility in 40% of IBS patients. Abdominal symptoms evoked by CRH in IBS patients lasted significantly longer than those in controls (p<0.05). CRH induced significant increases in plasma ACTH levels in both groups (p<0.001) and produced significantly higher plasma ACTH levels in IBS patients than in controls (p<0.001). Conclusion—Human intestinal motility is probably modulated by exogenous CRH. The brain-gut in IBS patients may have an exaggerated response to CRH.

Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome

Background and aims: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of α-helical CRH (αhCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. Methods: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of αhCRH (10 μg/kg). Results: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of αhCRH. Administration of αhCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. αhCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by αhCRH. Conclusion: Peripheral administration of αhCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.

Brain-gut response to stress and cholinergic stimulation in irritable bowel syndrome : a preliminary study

To investigate the influence of the brain-gut interactions on the pathophysiology of irritable bowel syndrome (IBS), we compared such patients (n = 10) with healthy control subjects (n = 11) by measuring the pressure of the colon and small intestine simultaneously with analysis of power spectrum of the electroencephalography (EEG) under mental stress and administration of neostigmine. Stress slightly increased the colonic motility index, reduced the percentage of alpha power, and increased the percentage of beta and theta power of the EEG in the patients with IBS more than in the controls (p < 0.05). The patients with IBS had a longer phase II (p < 0.01) and shorter phase I (p < 0.02) of fasting duodenal motor activity than the controls. Neostigmine (10 micrograms/kg) caused a significant difference in the colonic motility index (p < 0.01) and power spectra of EEG (p < 0.05) in the patients with IBS compared to the controls. Significant positive correlation was detected between colonic motility and power spectral change induced by stress (r = 0.46, p < 0.05) or neostigmine (r = 0.51, p < 0.01). These results suggest that patients with IBS have exaggerated responsivity of the gut and the brain to mental stress and cholinergic stimulation. Moreover, there is a possibility that these exaggerated responses are related.

Exaggerated motility of the descending colon with repetitive distention of the sigmoid colon in patients with irritable bowel syndrome

Background. Visceral hypersensitivity is one of the mechanisms of irritable bowel syndrome (IBS), but it does not explain the entire symptomatology, i.e., altered bowel habit with abdominal pain relieved by defecation. We tested our hypothesis that an abnormal link between luminal stimulation and mural response may have some role in the pathophysiology of IBS. Methods. Patients with IBS (n = 10, median 21 years old, 5 male patients, 5 female patients) and healthy control subjects (n = 10, median 21 years old, 5 men, 5 women) were studied. A manometric catheter with three transducers was inserted to the descending colon and a balloon was placed in the distal sigmoid colon. Another catheter with three transducers was inserted to the duodenum. After baseline for 30 min, the sigmoid colon was stimulated by balloon distention for 30 min followed by recovery for 30min. Balloon distention was repeated 100 times, and each stimulation consisted of a 5-s inflation and a 10-s deflation, with a volume of 50 ml maximum. The sensory threshold of balloon inflation was then examined, and plasma adrenocorticotropic hormone (ACTH) was measured with radioimmunoassay. Results. Repetitive colonie distention induced a significant increase in motility indices (mmHg s/s%) of the descending colon in the IBS patients (from 118 ± 25 to 333 ± 108, P < 0.05) but not of those in controls (from 90 ± 16 to 89 ± 19). A significant group difference (P < 0.05), period effect (P < 0.02), and group X period interactions (P < 0.01) were detected with two-way ANOVA. Duodenal motility indices in controls were significantly reduced by colonic distention (from 169 ± 25 to 104 ± 14, P < 0.01), but those in the IBS patients were not (from 156 ± 17 to 124 ± 20). The sensory threshold of balloon inflation in the IBS patients (74 ± 10 ml) was significantly lower than that in controls (125 ± 6 ml, P < 0.001). There was no significant difference in plasma ACTH levels between the IBS patients and controls. Conclusions. Repetitive distention of the distal sigmoid colon below the sensory threshold induced orad exaggerated motility of the colon in IBS patients. The distention inhibited motility of the small intestine in healthy subjects, but this inhibition was blunted in IBS patients. These results suggest that IBS patients may have not only visceral hypersensitivity, but also an abnormal intestinal reflex.

Abnormal Electroencephalogram in Irritable Bowel Syndrome

BACKGROUND Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain and abnormal bowel habits. IBS patients sometimes complain of sleep disturbance, depression, and various autonomic symptoms. Our hypothesis is that the central nervous system (CNS) might play a role in the pathogenesis of IBS. METHODS We conducted two experiments using an electroencephalogram (EEG) to evaluate brain activity while at rest and during mental arithmetic stress with pharmacologic neostigmine administered to IBS patients. The first experiment was conducted on 48 conscious and relaxed patients (24 IBS patients and 24 normal controls). EEG recordings were evaluated for visual and power spectrum data. In the second experiment colonic manometric studies combined with EEG recordings were performed in 21 of 24 IBS patients and 8 of 24 normal controls under mental arithmetic stress and the administration of neostigmine. RESULTS Inspection of the EEG showed significantly greater EEG abnormality in the IBS patients (29.2%) than in the controls (4.2%) (P < 0.02). In the power spectrum analysis of the EEG the IBS patients showed significantly greater beta power percentage than did the normal subjects (P < 0.02). A significant positive correlation was observed between the colonic motility index and beta power percentage after the administration of neostigmine, 10 microg/kg, only in the IBS patients (P < 0.05). CONCLUSION A brain dysfunction as indexed by the EEG suggests an electrophysiologic brain-gut interaction in IBS.

Impact of stress on alcoholic liver injury; a histopathological study.

Certain behaviors can have an influence on the cause and progression of liver disorders. To clarify the relation between histopathological change of the liver and psychosocial stress, behavioral traits, and psychological state, patients with fatty liver (n = 14) were compared with patients with chronic hepatitis (n = 16). Both groups were alcohol-induced without other causes and consumed the same dose of alcohol. By morphometric methods, fat deposit ratio (FDR) and degree of liver damage (DLD) which reflects lobular fibrosis, inflammatory cell infiltration, and necrosis were evaluated. Life Change Unit scores from the Social Readjustment Rating Scale were significantly higher in chronic hepatitis than in fatty liver (p less than 0.001). DLD was significantly correlated with Life Change Unit (r = 0.59, p less than 0.01). It is suggested that psychosocial stress is one of the aggravating factors of fibrosis and inflammatory change of the liver which is previously damaged by alcohol in man just like the rat liver following stress.

Case Report: Reversal of Severe Leukopenia by Granulocyte Colony-Stimulating Factor in Anorexia Nervosa

Recent attempts to reduce weight by patients with anorexia nervosa have sometimes led to life-threatening hematologic complications. This report describes an instance in which a patient with anorexia nervosa and pancytopenia drastically improved with treatment that included administration of granulocyte colony-stimulating factor. The patient had lost 27 kg of body weight within 8 months. Even after admission, the blood cell count continued to decrease rapidly as follows: platelet, from 244 x 10(3)/microliters to 44 x 10(3)/microliters; erythrocyte, from 4.04 x 10(6)/microliters to 2.58 x 10(6)/microliters; and leukocyte, from 4.8 x 10(3)/microliters to 1.6 x 10(3)/microliters (granulocyte, 0.8 x 10(3)/microliters). Complications included pneumomediastinum, pneumothorax, purpura, petechiae, hepatomegaly, fever, gangrenous stomatitis, and somnolence. Bone marrow aspiration disclosed absence of fat cells, marrow hypoplasia, and infiltration of the mature lymphocytes. Intravenous hyperalimentation, blood transfusion, gamma-globulin, and antibiotics were administered, but leukopenia and fever remained. However, administration of recombinant human granulocyte colony-stimulating factor dramatically reversed the leukopenia and fever. With careful nutrition therapy, the patients blood cell count and bone marrow normalized by the time of discharge. It was concluded that severe hematologic disorders may occur in patients with anorexia nervosa, and advanced treatment may be required to save the patients life.