April 1995
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Motility and Nerve-Gut Interactions
INTESTINAL DYSMOTILITY IN HUMAN IMMUNODEFICIENCY VIRUS (HIV) SEROPOSITIVE SUBJECTS WITH DIARRHOEA. P J Neild, D F Evans*, F D Castillo*, D.L.Wingate*, B G Gazzard. HIV Uni% Chelsea and Westminster Hospital and *GI Science Research Unit, London Hospital Medical College, London, UK. Chronic diarrhoea is a common and debilitating problem in Human Immunodeficiency Virus seropositive (HIV+) individuals and its pathogenesis remains poorly understood. There is evidence of submucosal enteric nerve disruption, and. in addition, HIV infection is associated with autonomic dysfunction. In. this study we tested the hypothesis that, in HIV+ individuals with diarrhoea, gut motility is altered as a result of neurological dysfunction. Methods: 8 H1V+ subjects with chronic diarrhoea and 17 healthy controls were studied by intraluminal ambulatory manometry. A triple sensor strain gauge catheter was introduced transnasally and positioned fluoroscopically at the level of the Ligament of Treitz. Pressure was recorded for 24 hours using a miniature solid-state data logger.. Data was downloaded to diskettes and we analysed, using validated software, the 8 hour nocturnal fasting period, and the response tO meals. Results: The number of migrating motor complexes (MMCs) during the nocturnal fasting period was increased in HIV+ subjects, compared with controls. The amplitude of MMC Phase II (P2) was decreased, though frequency and duration were the same. The duration of MMC Phase III (P3) was decreased in HIV+ subjects, but amplitude, frequency and propagation velocity were not affected. The time from meal to the first P3 was decreased in HIV+ subiects. Median (interquartiles) Control HIV+ P2 amp/mm Meal to P3/min
No. of MMCs/Shr P3 dur/min
17 (15-I8)
13 (13-13.5)**
327 (276-375)
225 (87-300)**
4 (3-5)
7 (5-9)*
5.6 (5.3-7.2)
4.6 (4.5-4.7)*
*P<.05, **P<.005 (Mann-Whitney U Test) Conclusion: There are significant differences in upper GI motility between HIV+ subjects with diarrhoea and healthy controls, both in the fasting and fed state. In neuropathy of the myenteric plexus, diminished incidence, prolongation and slow migration of P3 are prominent. In contrast, P3 is relatively normal in HIV+ subjects, but the impaired response to food, similar to that reported in vagotomized patients, suggests an extrinsic autonomic neuropathy.
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I N F L U E N C E OF I N T E R F E R O N - ~ T R E A T M E N T ON GASTRIC EMPTYING IN PATIENTS WITH CHRONIC HEPATITIS C. H. Nishibayashi, S. Kanayama, T. Shinomura, Y. Higashimoto, Y. Miyazaki, S. Kawata , Y. Matuzawa. Second Dept. of Internal Medicine , Osaka University School of Medicine, Osaka, Japan. Although Interferon-Or (IFN-o~) is a powerful toot in the treatment of patients with chronic hepatitis C , it often brings dyspeptic symptoms, requiring the administration of prokinetic drugs. This suggests that IFN-~ may influence gastric emptying. The AlMs of this study are to investigate the influence of IFN-cx on gastric emptying and evaluate the effect of the prokinetic drug ,cisapride, on gastric emptying and dyspeptic symptoms in patients with IFN-cx treatment. METHODS : Fourteen patients with chronic hepatitis C ( 6F : 8M ) who were received 6 million units of recombinant human IFN-0~ ( Roche Takeda ) daily for 2weeks were divided into cisapride group ( 4F : 3M ) and control group ( 2F : 5M ). The cisapride group were administrated 7.5rag of cisapride daily for a week from one week after the beginning of IFN treatment. In each group, gastric emptying and dyspeptic symptoms were evaluated before IFN treatment, one week and two weeks after the beginning of 1FN treatment. Gastric emptying was evaluated by sulfamethizole capsule method ( Dig Dis Sci 39:2056-2061,1994 ). The area under the sulfamethizole concentration-time curve up to 120 minutes (AUC120), which was in a good negative correlation with gastric emptying T112 measured by radioscintigraphie method, was used as an indicator of gastric emptying. All patients had no dyspeptic symptoms before 1FN treatment. RESULTS : In each group, gastric emptying at one week after the beginning of IFN treatment was significantly delayed compared with that before IFN treatment. In the cisapride group, gastric emptying at two weeks after the beginning of IFN treatment was significantly improved compared with that at one week.But in the control group, gastric emptying did not change (table). AUC120(t~-h/ml) BEFORE ONE WEEK TWO WEEKS Cisapride IFN IFN+Cisapride Group (n=7) 20.5_+1.8 14.8_+2.0" 18.7_+1.7"* Control IFN IFN Group (n=7) 23.4_+4.2 12.7_+l.8" 12.8_+2.0 (mean_+SE, *P<0.05 vs before, **P<0.05 vs one week) At one week after the beginning of IFN treatment, 5 patients had dyspeptic symptoms in the cisapride group and 3 patients had dyspeptic symptoms in the control group. At two weeks after the beginning of the IFN treatment, the dyspeptic symptoms were successfully relieved in two of the five patients in the cisaprid group, while no improvements were observed in the control group. CONCLUSION: 1) IFN-c~ treatment delays gastric emptying of patients with chronic hepatitis C. 2) Cisapride improves delayed gastric emptying and dyspeptic symptoms due to IFN-ct treatment.
A657
ALTERED E S O P H A G E A L M U C O S A L INNERVATION IN P A T I E N T S W I T H ESOPHAGITIS. M. Newton , P.O. Soediono, P. Milner, W.R. Burnham, M.A. Kamm, G. Burnstock. University College, St Mark's & Oldchurch Hospitals, London, UK.
Little is known about esophageal mucosal innervation and whether alterations contribute to both the local inflammation or the abnormal sphincter control in patients with reflux disease. Methods: Esophageal mucosal biopsies w e r e obtained from 10 healthy controls, the inflamed & uninflamed mucosa of 9 patients with reflux disease, and 5 patients with healed esophagitis. All b i o p s i e s contained epithelium and the majority also contained some lamina propria. Distribution of the neuronal marker protein gene product 9.5 (PGP), and neuropeptides calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP) and vasoactive intestinal polypeptide ( r i P ) were investigated by immunohistochemistry. Density of innervation was a s s e s s e d by the proportion of papillae in each esophageal mucosal biopsy containing immunoreactive fibres. Results: Nerve fibres immunoreactive to the neuropeptides w e r e found in the subepithelium and mucosal papillae. In decreasing order the greatest proportion of fibres were immunoreactive to NPY, SP, CGRP, and VIP, except in inflamed tissue. When compared with controls, uninflamed and h e a l e d tissue, inflamed esophagitis tissue showed a significant increase in the proportion of PGP 9.5 (controls 34% papillae, uninflamed 38%, healed 46%, inflamed 75%, p<0.05) and VIP (10%, 7%, 9%, 58%, p<0.05) immunoreactive fibres. Other n e u r o p e p t i d e s showed no proportional change in inflammation. Conclusions: The innervation of the esophageal mucosa is not altered in uninflamed tissue in patients with reflux disease, but alters in response to inflammation. The main observed change appears to involve increases in VIP immunopositive nerve fibres.
PULSED DOPPLER ULTRASONOGRAPHIC ASSESSMENT OF GASTRIC EMPTYING. K. Nishihara~ T. Yagyu, S. Kanemura, T. Suzuki. Dept. of Surgery II, University of Yamaguchi, Yamaguchi, Japan We investigated postprandial changes on portal Bow in normal subjects and in patients with several upper gastrointestinal operations, with the aim to clarify the relationship between the postprandial portal hemodynamics and gastric emptying. Subjects and methods: Twenty healthy volunteers and 38 patients participated in this study. Sixteen patients had undergone pylorus preserving pancreatoduodenectomy (PPPD); 6 had undergone standard pancreatoduodenectomy (STPD); 8 had undergone distal partial gastrectomy (PG); and 8 patients had undergone total gastrectomy (TG). A 250 ml of liquid meal (YH-80, Meiji Milk Co., Ltd., Japan) was ingested within 5 rain, and the subjects remained supine in bed until the end of the examination. Informed consent was obtained from all subjects. Portal blood flow measurements were performed with a pulsed Doppler apparatus (Aloca SSD 2000) in the right anterior portal branch. Maximum velocity was measured prior to ingestion, and at 5, 10, 15, 20, 25, 30, 45, 60, 75, and 90 min after ingestion. At each time period, mean velocity was obtained by averaging three consecutive measurements of the maximum velocity. The postprandial mean velocity we[e expressed as percentage of the fasting value ( mean ± SEM). The values were compared by means of Scheffe's test. Differences were considered significant at p<0.05. Results: In normal subjects, the mean velocity peaked 20 min after ingestion (174 --+11%) and gradually decreased (135 ± 7% at 90 rain). In patients with TG, the mean velocity peaked 10 rain after ingestion (176 ± 21%) and decreased rapidly (110 ±4% at 90 min). In patients with STPD and PG, it showed almost the same tendency with that in patients with TG. On the contrary, the mean velocity in patients with PPPD peaked 20 min after ingestion, although, the peak value (133 ± 9%) was significantly less than that in the other groups. Conclusions: It was easily poslulated that more rapid increase in the velocity after a meal in patients with gastrectomy (TG, PD, and STPD) was induced by the rapid delivery of a meal into the upper intestine, on the contrary, lesser increase in the velocity in patients with PPPD was caused by delayed gastric emptying. Our results demonstrated that pulsed Doppler ultrasonography could be used for real-time and simple study of gastric emptying.