Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease--the role of transient elastography and plasma cytokeratin-18 fragments.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects 15-40% of the general population. Some patients have non-alcoholic steatohepatitis (NASH) and progressive fibrosis, and would be candidates for monitoring and treatment. AIM: To review current literature on the use of non-invasive tests to assess the severity of NAFLD. METHODS: Systematic literature searching identified studies evaluating non-invasive tests of NASH and fibrosis using liver biopsy as the reference standard. Meta-analysis was performed for areas with adequate number of publications. RESULTS: Serum tests and physical measurements like transient elastography (TE) have high negative predictive value (NPV) in excluding advanced fibrosis in NAFLD patients. The NAFLD fibrosis score comprises of six routine clinical parameters and has been endorsed by current American guidelines as a screening test to exclude low-risk individuals. The pooled sensitivities and specificities for TE to diagnose F ≥ 2, F ≥ 3 and F4 disease were 79% and 75%, 85% and 85%, and 92% and 92% respectively. Liver stiffness measurement often fails in obese patients, but the success rate can be improved with the use of the XL probe. A number of biomarkers have been developed for the diagnosis of NASH, but few were independently validated. Serum/plasma cytokeratin-18 fragments have been most extensively evaluated and have a pooled sensitivity of 66% and specificity of 82% in diagnosing NASH. CONCLUSIONS: Current non-invasive tests are accurate in excluding advanced fibrosis in NAFLD patients, and may be used for initial assessment. Further development and evaluation of NASH biomarkers are needed.

Twenty-year audit of percutaneous liver biopsy in a major Australian teaching hospital.

BACKGROUND: To examine the changes in indications, patient characteristics, safety and outcomes in consecutive patients undergoing percutaneous core liver biopsies in a major Australian teaching hospital over a period of two decades. METHODS: A retrospective audit was carried out on all percutaneous core liver biopsies from a single institution between 1996 and 2005. This was combined with 10 years of data already reported on for the years 1986-1995 to detect trends in indications and outcomes. RESULTS: Medical records from 1398 patients were included for analysis. Over a 20-year period, the most common indications for liver biopsy were hepatitis C (37.8%), hepatitis B (26.4%) and abnormal liver function tests (22.2%). Twelve major complications (1.0%) were seen; 10 episodes of haemorrhage, 1 bile leak and 1 visceral perforation. Seven of these patients had an abnormal baseline coagulation profile; a significant risk for major haemorrhage (P < 0.001), resulting in three deaths. All deaths occurred in inpatients with major comorbidities. Minor complications occurred in 13.6% of patients, with multiple passes a significant risk factor. Whereas the overall major and minor complication rates were independent of operator experience inadequate specimens were more frequently obtained by the registrar. CONCLUSION: This large series extending over two decades shows that despite advances in biopsy techniques, the rates of both minor and major complications remain significant. Of particular concern are the procedure-related deaths. Identifying factors that may increase risk requires further scrutiny and careful patient selection needs to be undertaken.

The C-caffeine breath test distinguishes significant fibrosis in chronic hepatitis B and reflects response to lamivudine therapy.

BACKGROUND: The 13C-caffeine breath test is a non-invasive, quantitative test of liver function. AIM: To determine the utility of the 13C-caffeine breath test in chronic hepatitis B virus and its ability to monitor response to lamivudine. METHODS: Forty-eight chronic hepatitis B virus patients and 24 controls underwent the 13C-caffeine breath test. In 28 patients commenced on lamivudine, 13C-caffeine breath tests were performed at 1 week (n = 12) and after 1 year of therapy. RESULTS: Patients with Metavir F0-1 fibrosis (2.30 +/- 1.02 Delta per thousand per 100 mg caffeine) had a 13C-caffeine breath test similar to controls (2.31 +/- 0.85, P = 0.96). However, patients with F2-3 fibrosis (1.59 +/- 0.78, P = 0.047) and cirrhotic patients (0.99 +/- 0.33, P = 0.001) had a decreased 13C-caffeine breath test. Fibrosis correlated best with the 13C-caffeine breath test (r(s) = -0.62, P < 0.001). The 13C-caffeine breath test independently predicted significant (F > or = 2) and advanced (F > or = 3) fibrosis and yielded the greatest area under the receiver operating characteristic curve (0.91 +/- 0.04) for predicting advanced fibrosis. The 13C-caffeine breath test was unaltered by 1 week of lamivudine but improved by 61% (P < 0.001) in responders to long-term lamivudine, whereas in those with viraemia and elevated alanine aminotransferase, values remained stable or deteriorated. CONCLUSION: The 13C-caffeine breath test distinguishes chronic hepatitis B virus-related fibrosis and detects improvement in liver function in response to long-term lamivudine.

Patients with gastro-oesophageal reflux disease and cough have impaired laryngopharyngeal mechanosensitivity.

BACKGROUND: Laryngopharyngeal sensitivity (LPS) is important in preventing pulmonary aspiration and may be impaired by anaesthesia and stroke. It has been suggested that gastro-oesophageal reflux disease (GORD) may also impair LPS, although the underlying mechanism is unclear. The aim of this study was to compare LPS in patients with chronic cough and GORD with healthy subjects and to determine the effect of laryngopharyngeal infusions of both acid and normal saline on LPS. METHODS: Fifteen patients with chronic cough and GORD and 10 healthy subjects without GORD underwent LPS testing using the fibreoptic endoscopic evaluation of swallowing with sensory testing (FEESST) technique. LPS, as measured by the lowest air pressure required to elicit the laryngeal adductor reflex (LAR), was determined both before and after laryngopharyngeal infusions of normal saline and 0.1 N hydrochloric acid performed on separate days. RESULTS: The mean baseline LAR threshold of the patient group was significantly higher (9.5 mm Hg, range 6.0-10.0) than in normal subjects (3.68 mm Hg, range 2.5-5.0; p<0.01). Retest thresholds were not significantly different. In normal subjects LAR thresholds were significantly raised after acid but not after saline infusion (p = 0.005). There were no complications associated with the procedure. CONCLUSIONS: Patients with cough and GORD have significantly reduced LPS to air stimuli compared with healthy subjects which could potentially result in an increased risk of aspiration. Exposure to small amounts of acid significantly impaired the sensory integrity of the laryngopharynx.

Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum.

Herbal preparations are widely available and generally regarded by the public as harmless remedies for a variety of medical ailments. We report the first case in Australia of acute hepatitis associated with the Chinese herbal medicine Shou-Wu-Pian, prepared from Polygonum multiflorum. Cholestatic hepatitis developed in a Chinese woman taking this preparation for the greying of her hair, and liver biopsy was consistent with a toxic reaction. Clinical and biochemical resolution occurred following cessation of the drug.

Aspartate aminotransferase: alanine aminotransferase ratio in chronic hepatitis C infection: is it a useful predictor of cirrhosis?

BACKGROUND: The clinical usefulness of the ratio of serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) has been explored in several liver disorders. It has been suggested that in patients with chronic hepatitis C virus (HCV) infection an AST:ALT > or = 1 has 100% specificity and positive predictive value in distinguishing cirrhotic from non-cirrhotic patients. Such statistical certainty attached to a simple biochemical test merits further evaluation. The present study, therefore, assessed the AST:ALT in patients with chronic HCV infection to determine the validity of the ratio in predicting cirrhosis and to correlate the ratio with the histological grade of necroinflammatory activity and fibrosis. METHODS: A retrospective analysis of 153 patients with chronic HCV infection was conducted. Serum biochemistry had been obtained within a mean of 4 weeks of liver biopsy. The histology was scored in terms of activity and fibrosis as described by Scheuer and correlated with AST:ALT. RESULTS: In 30 patients with cirrhosis, the mean AST:ALT (0.99 +/- 0.06) was higher than in 123 patients without cirrhosis (0.60 +/- 0.02; P < 0.001). A ratio > or = 1 had 95.9% specificity and 73.7% positive predictive value in distinguishing cirrhotic from non-cirrhotic patients, with a 46.7% sensitivity and 88.1% negative predictive value. The ratio also parallelled the Scheuer score with respect to fibrosis but not with respect to inflammation. CONCLUSION: Although relatively insensitive, an AST:ALT > or = 1 is highly specific but not diagnostic for the presence of cirrhosis in patients with chronic HCV infection. The ratio reflects the grade of fibrosis in these patients.

Obstructive sleep apnea and gastroesophageal reflux.

A number of recent studies have described the presence of significant gastroesophageal reflux (GER) in patients with obstructive sleep apnea (OSA). The aims of our studies were to determine the prevalence of this in a controlled population and to investigate the potential for a causal relationship between the two entities by determining whether therapy of OSA altered GER parameters, and vice versa. All patients presenting to our sleep laboratory for screening polysomnography underwent distal esophageal pH monitoring simultaneously with polysomnography. Control subjects were selected if the apnea-hypopnea index (AHI) was <5.0, and patients were selected if AHI was >15.0. Fourteen subjects with OSA undertook a second polysomnographic study including distal esophageal pH monitoring, with nasal continuous positive airway pressure (nCPAP) intervention. Twelve subjects with proven OSA took part in a randomized, placebo-controlled, double-blinded, parallel group study of the effect of antireflux therapy (nizatidine) on OSA parameters. In 63 patients and 41 controls, we found that patients with OSA had significantly more GER events than controls as measured by number of reflux events over 8 hours (115 vs 23; P <0.001), and percent of time spent at pH <4.0 (21.4% vs 3.7%; P <0.001). In patients with proven OSA, 53.4% of GER episodes were temporally related to apneas or hypopneas. Less than half (46.8%) of all apneas were temporally related to acid reflux, and only 43.8% of arousals were related to reflux events. In the therapeutic trials, nCPAP reduced GER parameters in both patients with OSA and without OSA, suggesting a nonspecific effect. Antireflux therapy (nizatidine) reduced arousals but not apnea-hypopnea index in patients with OSA. Patients with OSA have a higher prevalence of GER than matched control subjects. Nasal CPAP reduces GER parameters nonspecifically, and thus the role of OSA in the pathogenesis of GER remains unclear. GER, however is likely to be important in the pathogenesis of arousals, but there is no evidence that it is involved in the pathogenesis of apneas.

The effect of dosing with omeprazole on the accuracy of the 13C-urea breath test in Helicobacter pylori-infected subjects.

BACKGROUND: The 13C-urea breath test (13C-UBT) is an accurate means of Helicobacter pylori diagnosis. However, proton pump inhibitors may suppress H. pylori and cause false negative results. AIM: To study the kinetics of H. pylori suppression by omeprazole during and after short-term use. METHODS: Volunteers underwent a baseline 13C-UBT (13C-urea 100 mg). H. pylori-positive subjects took omeprazole 20 mg daily for 14 days. Those who remained 13C-UBT positive (delta13CO2 >/= 5) continued omeprazole for a further 14 days. 13C-UBTs were performed weekly on omeprazole and then every second day after it was stopped. False negatives occurred when delta13CO2 fell to < 5. RESULTS: In 25 H. pylori-positive subjects (mean age 43.9 +/- 2.4 years; 21 females, 4 males) the mean baseline delta13CO2 was 28.1 +/- 3.4. False negative breath tests occurred in three subjects after 7 days of omeprazole and in a further four subjects after 14 days. A further six subjects developed negative tests between Days 14 and 28. Following cessation of omeprazole, the 13C-UBT became positive again in 12/13 subjects within 4 days and in all within 6 days, with a mean recovery to 99.9 +/- 18.6% of baseline delta13CO2. CONCLUSIONS: False negative 13C-UBTs are common during treatment with omeprazole and occur after as little as 7 days. Return to positive test results is rapid after cessation of omeprazole. These findings are relevant to the timing of testing in clinical practice.

The impact of short-term ranitidine use on the precision of the 13C-urea breath test in subjects infected with Helicobacter pylori.

BACKGROUND: The 13C-urea breath test (13C-UBT) is a very accurate method of Helicobacter pylori diagnosis with a false-negative rate of 1-3%. However, the accuracy of the 13C-UBT is affected by potent acid inhibition with proton-pump inhibitors, which may suppress H. pylori and cause false-negative results. It is not known whether this occurs with less potent acid inhibition by H2-antagonists and any effect may be important clinically. OBJECTIVE: To determine the kinetics of 13CO2 excretion in H. pylori infected subjects during and after short-term ranitidine use. METHODS: Volunteers underwent a baseline 13C-UBT (positive: delta13CO2 > or = 5.0; negative: < or = 3.5; indeterminate: > 3.5 to < 5.0). Infected subjects took ranitidine 300 mg each evening for up to 28 days. 13C-UBTs were performed at weekly intervals and then every other day after ranitidine was ceased. If the 13C-UBT remained positive after 14 days, ranitidine was continued for a further 14 days. RESULTS: Thirty-one subjects were studied (mean age 40.4 +/- 2.1 years; 23 female/8 male; mean baseline delta13CO2 27.3 +/- 2.5). In 28 subjects the 13C-UBT remained positive during ranitidine use. The mean delta13CO2 rose to 124% (P< 0.06) and 121% (P < 0.05) of baseline at 14 and 28 days respectively. In two subjects, the delta13CO2 became indeterminate at day 7 (delta13CO2 4.3 and 3.8). In one of these, return to a positive value (delta13CO2 13.6; 103% of baseline) occurred while still on ranitidine. The other subject became positive again by day 3 off ranitidine (17.8; 119% of baseline). One subject had a transiently negative test after 21 days and this became positive again while still taking ranitidine. CONCLUSIONS: Ranitidine has a minimal effect on the 13C-UBT. The rate of indeterminate or false-negative tests is no greater than in patients on no anti-secretory medication.

Prevalence and demographic determinants of metronidazole resistance by Helicobacter pylori in a large cosmopolitan cohort of Australian dyspeptic patients.

BACKGROUND: The pre-treatment sensitivity of Helicobacter pylori to metronidazole is a key determinant of successful eradication therapy and should influence local choice of therapy. However, there are few data defining the prevalence of metronidazole resistance (MR) in Australia. AIM: To determine prospectively the prevalence and demographic determinants of MR in H. pylori isolates from a large and cosmopolitan cohort of dyspeptic patients in Sydney. METHODS: Consecutive dyspeptic patients undergoing endoscopy had gastric biopsies for histology, urease test and culture. Metronidazole resistance was determined by E-test after subculture. An MIC > 8 micrograms/mL defined MR. Patient age, gender, birthplace and history of previous nitroimidazole use were recorded. RESULTS: In 732 patients, H. pylori was present in 46.4%. Culture was successful in 81% and subculture for MR in 88% of these. In 237 evaluable patients the overall MR rate was 59.1%. Five patients had had prior triple therapy for H. pylori (of which four of five had MR). Therefore, the primary MR rate in the study population was 58.6% (136/232). MR was more prevalent in younger patients (p = 0.0002). The MR rate was 70.4% in patients 18-39 years, 66.7% in those aged 40-59 years and lowest (38.9%) in those 60 years or older (p = 0.002). The MR rate was highest in patients born in Southeast Asia (72.8%, 59/81) and significantly higher than in Australian born (48.1%, 26/54), or Southern European (46.2%, 24/52) born patients (p = 0.002). There was no gender difference. Logistic regression to determine the impact of each variable (birthplace, age and gender) on MR identified Southeast Asia birthplace as a factor associated with greater likelihood of harbouring an MR isolate (OR 1.88, p = 0.02). Southern European born patients had the lowest risk of MR (OR 0.70, p = 0.02) as did patients older than 60 years (OR 0.56, p = 0.04). A definite history of prior metronidazole use was infrequent and not predictive of MR. CONCLUSIONS: While a high rate of MR is not unexpected in patients born in developing countries, the high rate in Australian born patients is surprising and of concern. This may relate to the high local usage of nitroimidazoles as monotherapy and has important implications for the effectiveness of metronidazole containing triple therapies.

Staging of oesophageal carcinoma by endoscopic ultrasound: preliminary experience.

BACKGROUND: Endoscopic ultrasound (EUS) is a relatively recent imaging modality that is capable of visualizing oesophageal tissue layers and para-oesophageal structures. Current pre-operative staging of oesophageal cancer is less than satisfactory, and a modality which may improve pre-operative staging, thus allowing a more rational approach to choice of treatment, may be a welcome addition to current techniques. The purpose of the present study was to evaluate the accuracy of EUS in the staging of oesophageal carcinoma in a consecutive cohort of patients. METHODS: Forty-three patients with oesophageal cancer were prospectively staged with EUS using the radial scanning Olympus EUM-3 echo-endoscope. In the 28 patients who underwent surgery EUS staging was correlated with operative and histological findings to evaluate the EUS accuracy rate of assessing tumour depth (T stage), and the presence of nodal involvement (N stage) using internationally accepted TNM staging criteria. RESULTS: Endoscopic ultrasound accuracy rates for overall T-staging was 61% whereas that of N-staging was 75%. The overall TNM pathological staging was 75% accurate by EUS. CONCLUSIONS: Compared to published literature figures for oesophageal staging by computed tomography scanning (39-54%) these results demonstrate that EUS has a reasonable accuracy rate for staging. Endoscopic ultrasound may prove to be a useful additional modality in the management of oesophageal cancer.

Pathogenesis of chronic persistent cough associated with gastroesophageal reflux.

It was previously shown that unexplained chronic cough is associated with asymptomatic gastroesophageal reflux. The aim of this study was to determine if distal esophageal acid is important in the pathogenesis of this cough. In 22 patients with cough and reflux as determined by 24-h ambulatory esophageal pH monitoring, distal esophageal acid perfusion was performed in a double-blind controlled fashion. Patients received both 0.1 N HCl and 0.9% saline for 15 min, in random order. Cough was recorded with a microphone and then computer analyzed. In 12 matched control subjects, 24-h ambulatory esophageal pH monitoring and distal esophageal acid perfusion studies were also performed. In patients, there was a significant increase in cough frequency, median (range): 36.5 (6 to 111) versus 8.3 (0 to 46)/15 min, p < 0.001, and amplitude, geometric mean (range): 85.2 (78.1 to 92.3) versus 73.1 (0.0 to 87.1) dB, p < 0.01, with HCl compared with saline. During HCl infusion, compared with control subjects, patients had more cough episodes, 36.5 (6 to 111) versus 0.0 (0 to 11)/15 min, p < 0.0001, with greater amplitude, 85.2 (78.1 to 92.3) versus 0.0 (0.0 to 79.6) dB, p < 0.001, but there was no difference in cough duration. We subsequently investigated whether inhibition of the induced cough was possible. In seven patients repeat esophageal acid perfusion was performed 15 min after the esophageal instillation of 4 ml of 4% lignocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of age, Helicobacter pylori infection, and gastritis with atrophy on serum gastrin and gastric acid secretion in healthy men.

Gastric acid secretion has been considered to decline with increasing age but this view is being re-evaluated as the importance of Helicobacter pylori infection emerges. This study aimed to determine the effect of age, H pylori, and gastritis with atrophy on the serum gastrin concentration, gastric secretory volumes, and acid output in healthy, asymptomatic men. Young men (mean (SD) age 22.9 (0.6) years; n = 22) were compared with old men (72.9 (1.2) years; n = 28) in respect of basal serum gastrin and basal, sham fed, pentagastrin stimulated maximal and peak acid secretion. Antral, corpus, and fundal biopsy specimens were taken for histology and H pylori status (histology, culture, and rapid urease test). H pylori associated gastritis was present in three of 22 young (13.6%) and 16 of 28 old (57.1%) men. Gastritis with atrophy was present in 11 old subjects, 10 of whom were H pylori positive. These subjects had higher mean (SD) serum gastrin concentrations than old subjects without atrophy and young subjects (61.8 (9.2); 40.0 (2.9); 36.8 (2.3) pmol/l respectively; p < 0.001). H pylori infected subjects had higher gastrin values than uninfected subjects, overall (55.3 (5.9); 36.0 (1.8) pmol/l; p < 0.001) and in subjects without atrophy (45.3 (4.2); 36.0 (1.8) pmol/l; p < 0.03). In subjects without H pylori infection, gastrin values did not differ with age (old 37.1 (1.7); young 35.4 (2.1) pmol/l). The maximal gastric secretory volume was lower in old subjects with atrophy. Acid output (mmol/h) in subjects with atrophy was lower than in subjects with no atrophy (basal: 3.0(1.1); 5.1(0.7); p=NS; sham led: 5.4 (1.4); 9.3 (0.8); p<0.02; maximal: 18.9 (4.0); 31.4(1.8); p<0.002; peak: 25.1(5.3); 43.4(2.7); p<0.003). However, acid secretion in old subjects without atrophy was not different to that in young subjects, irrespective of H pylori status. These results did not differ when acid output was expressed as mmol/h/kg lean body mass or mmol/h/kg fat free body weight. Using multiple linear regression analysis, gastritis with atrophy was the only factor that had an independent negative effect on acid secretion. In healthy men without atrophy, gastric acid secretion is preserved with ageing and is independent of H pylori status. Atrophy, which is closely related to H pylori infection, is associated with a decline in acid secretion. Increased basal serum gastrin is related to both atrophy and H pylori infection but not to ageing per se.

Chronic persistent cough and clearance of esophageal acid.

Unexplained chronic persistent cough has been shown to be associated with increased episodes of otherwise asymptomatic gastroesophageal reflux; however, normal subjects without cough also exhibit some reflux. We postulate that the prompt clearance of refluxed acid from the esophagus may play an important role in the prevention of cough, and we sought to determine if patients with chronic cough have impaired clearance. Thirty patients with unexplained chronic cough underwent 24-h ambulatory esophageal pH monitoring. Compared to 12 matched control subjects, patients experienced significantly more episodes (all values expressed as median [range]) of reflux per 24 h (88.3 [5.0 to 338.0] vs 5.7 [0 to 13.0]; p < 0.0001) and had impaired clearance of esophageal acid as measured by the duration of individual reflux episodes (3.0 [0.1 to 20.5] min per reflux vs 0.7 [0 to 2.5] min per reflux; p < 0.01). We conclude that patients with chronic persistent cough have impaired clearance of esophageal acid.

Chronic persistent cough and gastro-oesophageal reflux.

Chronic cough persisting for two months or more that remains unexplained after extensive investigations is a common clinical problem. The purpose of this study was to determine whether such cough is associated with otherwise asymptomatic gastro-oesophageal reflux. Thirteen patients with chronic persistent cough that was unexplained after a standard diagnostic assessment were identified. All were non-smokers. The mean (SE) duration of cough was 17.8 (8.0) months. Ten had never had reflux symptoms and three had had mild symptoms only after the onset of the cough. All the patients completed standardised cough diary cards for eight weeks and underwent 24 hour ambulatory oesophageal pH monitoring. A reflux episode was defined as a fall in oesophageal pH to below 4.0. Nine control subjects were matched for age, lung function, and body mass index. The patients experienced significantly more episodes of reflux per 24 hours than the controls (115.8 (SE 31.7) versus 4.7 (1.4) and longer reflux episodes (15.5 (5.8) versus 1.7 (0.5) minutes), and the oesophageal pH was below 4.0 considerably longer (84.5 (20.2) versus 3.8 (1.3) minutes). Cough occurred simultaneously with 13% (2.2%) of reflux episodes and within five minutes in another 35% (5.8%) of episodes, whereas gastro-oesophageal reflux occurred simultaneously with 78% (5.5%) of cough episodes and within five minutes in another 12% (2.3%) of episodes. It is concluded that chronic persistent cough that remains unexplained after a standard diagnostic assessment is associated with otherwise asymptomatic gastro-oesophageal reflux. It is suggested that a self perpetuating mechanism may exist whereby acid reflux causes cough via a local neuronal oesophageal-tracheo-bronchial reflex, and the cough in turn amplifies reflux via increased transdiaphragmatic pressure or by inducing transient lower oesophageal sphincter relaxation. Further study of this mechanism and the role of specific antireflux treatment in chronic persistent cough is warranted.

Development of the extrinsic sympathetic innervation to the enteric neurones of the rat small intestine.

The development of the sympathetic control of motility of the small intestine of the rat has been studied over the early postnatal period. An inhibition of spontaneous motility was recorded in response to stimulation of the mesenteric paravascular nerve bundles as early as 3-4 days postnatal. At this time, the ganglia of the myenteric plexus were well supplied with noradrenergic nerve fibres, while not all of the ganglia of the submucous plexus were contacted by fibres until 6 days postnatal. The sympathetic innervation to the submucous arteries developed even later and at 9 days postnatal was still less dense than in adults. The onset of sympathetic function in the gut preceded that in the mesenteric arteries by several days. These results further support the hypothesis that the sympathetic neurones supplying the enteric ganglia are a subpopulation of cells distinct from those supplying the blood vessels of the mesentery and submucosa.

Sympathetic postganglionic reinnervation of mesenteric arteries and enteric neurones of the ileum of the rat.

The reinnervation by sympathetic postganglionic noradrenergic nerve fibres of a mesenteric artery and the ganglionic plexuses of the mid ileum of young rats has been examined using both physiological and anatomical techniques at various times, up to 6 months, after the interruption of their nerve supply by a freezing technique. Reinnervation of the artery was extremely slow and even 6 months after the operation there were fewer fibres over the surface of the artery than before denervation. The responses to nerve stimulation were smaller than those recorded from control vessels. Two distinct post-junctional membrane potential responses to nerve stimulation were recorded from the arterial smooth muscle cells during the process of reinnervation. These responses were similar to those previously recorded during the development of the sympathetic innervation to mesenteric arteries. The responses within the gut wall to sympathetic postganglionic nerve stimulation reappeared by 3 weeks after the operation. At this time, however, a minority of ganglia had been reinnervated as judged by the histochemical localization of catecholamines. The sympathetic fibres reinnervating both the arteries and the intramural plexuses regenerated from the interrupted axons of the paravascular nerve trunks. There was little or no contribution to the reinnervation pattern as a result of sprouting of existing noradrenergic nerve fibres either on the artery proximal to the point of denervations or within adjacent segments of the gut wall.