Complications in surgery for Crohn's disease after preoperative antitumour necrosis factor therapy.

BACKGROUND: The use of biological therapy (biologicals) is established in the treatment of Crohn's disease. This study aimed to determine whether preoperative treatment with biologicals is associated with an increased rate of complications following surgery for Crohn's disease with intestinal anastomosis. METHODS: All patients receiving biologicals and undergoing abdominal surgery with anastomosis or strictureplasty were identified at six tertiary referral centres. Demographic data, and preoperative, operative and postoperative details were registered. Patients who were treated with biologicals within 2 months before surgery were compared with a control group who were not. Postoperative complications were classified according to anastomotic, infectious or other complications, and graded according to the Clavien-Dindo classification. RESULTS: Some 111 patients treated with biologicals within 2 months before surgery were compared with 187 patients in the control group. The groups were well matched. There were no differences between the treatment and control groups in the rate of complications of any type (34·2 versus 28·9 per cent respectively; P = 0·402), anastomotic complications (7·2 versus 8·0 per cent; P = 0·976) and non-anastomotic infectious complications (16·2 versus 13·9 per cent; P = 0·586). In univariable regression analysis, biologicals were not associated with an increased risk of any complication (odds ratio (OR) 1·33, 95 per cent confidence interval 0·81 to 2·20), anastomotic complication (OR 0·89, 0·37 to 2·17) or infectious complication (OR 1·09, 0·62 to 1·91). CONCLUSION: Treatment with biologicals within 2 months of surgery for Crohn's disease with intestinal anastomosis was not associated with an increased risk of complications.

Restorative proctocolectomy in patients with ulcerative colitis: a cross-sectional Danish population study on function and quality of life.

AIM: The study evaluated function and quality of life (QoL) in all patients having restorative proctocolectomy (RPC) in Denmark for ulcerative colitis (UC) from 1980 to 2010. Inclusion of all patients in one country has never previously been achieved. METHOD: All patients who had had a RPC in Denmark, from the first case in 1980 to the last case in 2010, were studied. A cross-sectional questionnaire survey was performed, and function and QoL were assessed using a standardized questionnaire - the Short-Form 36 (SF36) - and the inflammatory bowel disease questionnaire (IBDQ). RESULTS: The median duration of follow up was 11 (range, 1-30) years. Apart from deaths, pouch failures and research protection, data on function and QoL were obtained from 1047 (85%) of 1229 patients who had a functioning pouch at the time of the investigation. More female patients than male patients experienced urgency (56% vs 44%, P = 0.0021). The median number of bowel movements per 24 h was 7 (range, 1-23) in female patients and 6 (range, 1-20) in male patients (P < 0.001). Pad usage was more frequent among female patients than among male patients (62% vs 38%, P < 0.001). A higher incidence of major incontinence (P = 0.009) and use of pads (P = 0.01) was found among patients who had been operated on 21-30 years previously compared with those operated on 11-20 years previously. The prevalence of urgency was higher in patients who received surgery 0-10 years previously compared with 11-20 years previously (P = 0.009). The total IBDQ score was higher in male patients than in female patients (P < 0.001). Male patients scored higher in five of eight SF36 domains (P < 0.001). CONCLUSION: Female patients had more urgency, a higher frequency of defaecation and higher pad usage. This was associated with a reduced QoL. Nevertheless, RPC resulted in good function and a high degree of satisfaction in most patients.

Low complication rate after stoma closure. Consultants attended 90% of the operations.

AIM: To evaluate complications after stoma closure. METHOD: Using a retrospective review of 997 medical records, data were collected from all patients undergoing stoma closure at the Department of Surgery P, Aarhus University Hospital, Denmark, from 1996 to 2010. Patient data after Hartmann reversal and loop-ileostomy closure were compared. Data regarding the grade of the operating surgeon and assistant were extracted. RESULTS: Out of 997 patients, 700 (70.6%) had a loop-ileostomy closure and 172 (17.4%) had a Hartmann reversal. Postoperative mortality was 0.5%. Seven patients required re-operation (0.7%). Morbidity was registered in 31.9% of the patients, with 131 (13.1%) having early complications and 187 (18.8%) having late complications. Wound infection was the most frequent early complication, which occurred in 31 patients (3.1%). Only 10 patients (1%) had an anastomotic leak. Incisional hernia was the most frequent late complication, occurring in 92 patients (9.3%). A consultant attended 90% of the operations. Junior surgeons never performed stoma closure without supervision. Body mass index was significantly associated with the development of incisional hernia. Hartmann reversal was associated with higher rates of complications compared with loop-ileostomy closure. In patients with Hartmann reversal, stapled anastomosis was associated with stricture in 12 out of 95 cases (12.6%), whereas hand-sewn anastomosis was not associated with stricture (0 out of 64 patients; 0%; P < 0.05). CONCLUSION: Stoma closure is associated with low rates of leakage. A favourable case mix and high degree of consultant attendance may explain the good results.

Ileostomy revision using noncutting linear stapler.

OBJECTIVE: The study aimed to evaluate the outcome of ileostomy revision for retraction and prolapse using noncutting linear stapler. METHOD: Forty five patients undergoing a total of 94 stapled revisions between 1.1.1995 and 31.12.2005 were identified by the unique code for stomal revision. Medical records for all patients were examined. RESULTS: Thirty-five (77.8%) of the 45 patients were women. In 43 (95.6%), the indication was stomal retraction. Median follow-up was 28 months (2-122). One or more stapling procedures resulted in a normal stoma at follow-up in 18 (41.9%) of 43 patients treated for stomal retraction. When other types of repair were included, a normal stoma was achieved in 30 (69.8%) of 43 patients. Patients with a low BMI had the lowest success rate (44%), but none of the possible factors analysed for influence on success had a statistically significant impact. Two patients were treated for prolapse, and both needed other types of revision. CONCLUSIONS: Stapled ileostomy revision is easy to perform and has a low morbidity. Less than half the patients achieve a satisfactory long-term result after one or more stapling procedures. Many patients still benefit from other types of revision when stapling has failed.

A possible role of the L-arginine-nitric oxide pathway in the modulation of cholinergic transmission in the guinea-pig taenia coli.

1. The role of the L-arginine-nitric oxide (NO) pathway for non-adrenergic, non-cholinergic (NANC) relaxation of the guinea-pig taenia coli was studied by recording isometric tension in response to transmural field stimulation (TMS). 2. In preparations precontracted with prostaglandin F2 alpha (PGF2 alpha, 10(-6) M), TMS induced frequency-dependent responses of the muscle strips which could be abolished by tetrodotoxin (10(-6) M). NG-nitro-L-arginine (L-NNA, 10(-4) M), an L-arginine analogue, and potent inhibitor of NO synthesis, stereospecifically inhibited maximum relaxations, but did not shift the frequency-response curve. Pre-incubation with NG-nitro-D-arginine (D-NNA, 10(-4) M), atropine (10(-6) M) plus L-NNA (10(-4) M), or atropine (10(-6) M) alone, had no influence on the frequency-response characteristics. 3. L-NNA (10(-7)-10(-4) M) concentration-dependently inhibited relaxations in PGF2 alpha (10(-6) M) precontracted strips in response to TMS, but did not abolish relaxations. Preincubation with L-arginine (10(-4) M) inhibited these effects of L-NNA. L-NNA (10(-4) M) had no effect on the inhibitory response during TMS in strips preincubated with atropine (10(-6) M). 4. The relaxation induced by sodium nitroprusside and forskolin (10(-9)-10(-4) M) was not influenced by L-NNA (10(-4) M) preincubation as expressed by identical pD2 and Emax values. 5. Contractions induced by PGF2 alpha (10(-9)-10(-4) M) and carbachol (10(-9)-10(-4) M) were not affected by pretreatment with L-NNA (10(-4) M), was expressed by identical pD2 and Emax values. 5. Contractions induced by PGFA (10-1- 10-4M) and carbachol (10-1 0-4 M) were not affected by pretreatment with L-NNA (10-4 M), as expressed by identical pD2 and Em. values.6. In conclusion, the L-arginine-NO pathway seems to play a role in the NANC innervation of the guinea-pig taenia coli. The inhibitory effect of NO or a NO-like compound depends on the integrity of the cholinergic pathways and it is proposed that this compound exerts its effects prejunctionally on cholinergic nerves, by inhibiting the release of acetylcholine.

The role of the L-arginine-nitric oxide pathway in relaxation of the opossum lower oesophageal sphincter.

1. The role of the L-arginine-nitric oxide pathway in lower oesophageal sphincter (LOS) relaxation and oesophageal peristalsis was investigated. 2. Twenty four adult opossums were anaesthetized and the right vagus nerve was isolated in the neck and sectioned. Electrical stimulation, applied to the peripheral end of the nerve, resulted in a frequency-dependent relaxation of the LOS, and peristaltic and non-peristaltic contractions in the oesophageal body. 3. N omega-nitro-L-arginine (L-NNA, 10(-8)-10(-5) mol kg-1), an inhibitor of the L-arginine-nitric oxide pathway, inhibited LOS relaxation in a dose-dependent manner, but did not affect resting LOS pressure. At the highest dose of L-NNA no relaxation of the LOS was elicited in response to vagal stimulation. The effect of L-NNA, (10(-5) mol kg-1) was fully reversed by infusion of 10(-4) mol kg-1 L-arginine. Peristaltic velocity and amplitude of contractions in the oesophageal body were unaffected by L-NNA. 4. Infusion of sodium nitroprusside reduced LOS pressure to zero, and the drug was equally potent in control animals (-log ED50:8.1 +/- 0.2 mol kg-1) and in animals pretreated with L-NNA (-log ED50:8.2 +/- 0.3 mol kg-1). This suggests that the effect of L-NNA was not directly on guanylate cyclase. 5. A significant elevation of blood pressure was recorded after administration of L-NNA (10(-5) mol kg-1). 6. It is suggested that the L-arginine-nitric oxide pathway plays an important functional role for relaxation of the LOS, but not for oesophageal peristalsis. Whether the active substance is nitric oxide or a related nitroso-compound remains to be settled.

Pharmacological identification of different inhibitory mediators involved in the innervation of the internal anal sphincter.

1. Inhibitory non-adrenergic, non-cholinergic (NANC) responses were studied in isolated strips from the rabbit internal anal sphincter. 2. In the presence of atropine and guanethidine, transmural field stimulation induced frequency-dependent relaxations that reached a plateau at frequencies > or = 4 Hz. 3. These relaxations were inhibited by apamin (10(-6) M) and by N omega-nitro-L-arginine (L-NOARG, 10(-4) M). With these two substances in combination, relaxations were still seen in response to field stimulation, but only at frequencies > 2 Hz. 4. In the presence of both apamin (10(-6) M) and L-NOARG (10(-4) M), responses at high frequencies consisted of a fast relaxation followed by a slow return to prestimulus tension level. alpha-Chrymotrypsin hastens the return of tension to prestimulus level after high frequency stimulation. 5. Zinc-protoporphyrin IX, an inhibitor of haeme oxygenase, had a significant inhibitory effect on relaxations induced by transmural field stimulation. It was found, however, that responses to sodium nitroprusside and to isoprenaline (both 10(-9)-10(-4) M) were reduced comparably, indicating that the effect of zinc-protoporphyrin IX was unspecific. 6. It is concluded that pharmacological analysis allows identification of at least three distinguishable components of the inhibitory NANC innervation of the rabbit internal anal sphincter. The study does not allow conclusions about the role of carbon monoxide, a recently proposed mediator of NANC responses in opossum internal anal sphincter.

The effect of a new selective alpha 2-adrenoreceptor antagonist, idazoxan, and the agonist, clonidine, on fasting antroduodenal motility in healthy volunteers.

Studies were carried out on 16 healthy male volunteers to investigate whether intravenous administration of the alpha 2-adrenoreceptor antagonist, idazoxan, could affect fasting antroduodenal motility with and without administration of the agonist, clonidine. Contractile activity was recorded using an oral tube with perfused side holes positioned in the stomach and duodenum. Clonidine decreased antral contractile activity, an effect that idazoxan did not restore. Idazoxan alone did not affect antral motility. In the duodenum, clonidine decreased the number of contractions significantly and idazoxan restored them. Idazoxan alone did not increase duodenal motility but clonidine induced phase-III activity within the first 15 min after administration. The observations indicate that regulation of antroduodenal motility is influenced by alpha 2-adrenoreceptor drugs. Idazoxan may have potential as a motility restoring drug, for example, in postoperative ileus.

Response, relapse and mucosal immune regulation after infliximab treatment in fistulating Crohn's disease.

BACKGROUND: Infliximab reduces mucosal inflammation in some, but not all, patients with Crohn's disease. AIM: To monitor clinical data and changes in mucosal cytokine levels after infliximab treatment to identify differences between responders and non-responders. METHODS: Twenty-six patients with fistulating Crohn's disease received three infliximab infusions at weeks 0, 2 and 6. Follow-up was for 1 year and included clinical examination, colonoscopy, ano-rectal ultrasound and magnetic resonance imaging. Biopsies were taken at weeks 0, 8, 26 and 52. Cell cultures were established and analysed for tumour necrosis factor-alpha, interferon-gamma and interleukin-10 levels, and related to clinical status and fistula healing. RESULTS: Eleven of 15 patients (73%) with active disease (Crohn's disease activity index > 150) obtained remission (Crohn's disease activity index < 150) at 8 weeks. In in vitro cell cultures, there was reduced tumour necrosis factor-alpha and interleukin-10 production at week 26, with the latter persistent throughout the study period. When the disease deteriorated or relapsed, there was increased interferon-gamma production in in vitro cell cultures. Fistula healing was associated with reduced production of interferon-gamma, tumour necrosis factor-alpha and interleukin-10. CONCLUSIONS: Infliximab down-regulates mucosal immune activation in Crohn's disease. Monitoring of mucosal cytokine levels after infliximab treatment by whole biopsy cultures may be useful as interleukin-10, tumour necrosis factor-alpha and interferon-gamma production are different in responders and at relapse.

Motility regulating effects of galanin on smooth muscle of porcine ileum.

We studied the effect of synthetic porcine galanin on circular and longitudinal oriented strips of pig ileal muscle. Galanin 10(-11)-10(-6) M had no effect on resting tension in the two layers. In circular muscle precontracted with carbachol 10(-6) M, galanin dose-dependently inhibited the amplitude of contractions to a maximum of 33 +/- 8% at 10(-6) M. In longitudinal muscle the amplitude of contractions induced by carbachol 10(-7) M or transmural field stimulation increased after addition of galanin 10(-9)-10(-7) M to a maximum of 21 +/- 6%, while at higher concentrations inhibition occurred. Maximal inhibition was 36 +/- 14% at galanin 10(-6) M. Tetrodotoxin did not influence the effects of galanin in the preparations. The results indicate that in the homologous species galanin inhibits the circular muscle layer, possibly by a direct action on the smooth muscle. In the longitudinal muscle the effect of galanin is apparently excitatory. The inhibition observed with high concentration of galanin could be due to tachyphylaxis and desensitization. Alternatively, an additional population of low affinity, inhibitory receptors may exist.

Endothelium-dependent responses in small human mesenteric arteries.

The aim of the present study was to investigate the endothelial function in human mesenteric arteries with specific reference to defining the role of endothelium-derived nitric oxide (EDNO) and the endothelium-derived hyperpolarizing factor (EDHF). Isolated segments of small human mesenteric arteries (225-450 microm inner diameter) were mounted in organ baths for recording isometric tension. In arteries precontracted with U46619 (thromboxane A(2) analogue, 10(-7) M), endothelium-dependent relaxations were induced in a concentration-dependent manner by substance P and histamine. In normal Krebs solution the relaxations to substance P (10(-9) M) and histamine (10(-7) M) were not significantly affected by preincubation with N(omega)-nitro-L-arginine (L-NNA, 10(-4) M) or indomethacin (10(-5) M). When the preparations were exposed to a solution containing 60 mM KCl, stable contractions were induced, but relaxations could still be induced by substance P and histamine. When the arteries were further preincubated with L-NNA, the relaxations were almost abolished. A combination of apamin (3 x 10(-7) M) and charybdotoxin (10(-9) M) almost abolished relaxations in normal Krebs solution. It is concluded that isolated human mesenteric arteries respond to substance P and histamine with relaxations that are endothelium-dependent. Synthesis of both EDNO and EDHF seem important for these relaxations, whereas prostaglandins seem to be of minor importance.

Fetal weight estimation in twin pregnancies.

In this study the fetal weight was estimated by ultrasound measurements of the biparietal (BPD) and abdominal diameters (AD) in 154 consecutive twin pregnancies. In 80 twins an attempt to estimate fetal weight was made 0-4 days before delivery (26% of all twins examined). In 84% (67 infants) it was possible to estimate the fetal weight using the formula (0.0108 X AD1.72 X BPD0.99). 60% of the birth weights deviated less than 10% from the estimated fetal weight and 83% deviated less than 15%. The prediction error was nearly constant, expressed as percent of actual weight in the different weight groups (8.5-9.8%). In 19 LGA infants, 69% of the birth weights deviated less than 10% from the estimated fetal weight and 70% deviated less than 15%.

[Treatment of esophageal achalasia]. / Behandling af achalasia esophagi.

Achalasia is a motor disease of the oesophagus which can be treated surgically (myotomy), medically or by dilatation. After myotomy satisfactory results are obtained in 84%-95% of the patients. Unacceptable results are due primarily to gastro-oesophageal reflux, inadequate or healed myotomy. Dilatation provide good results in about 70% but generally repeated dilatation is required. The remaining 30% can usually be treated surgically. Dilatation is complicated by perforation in about 3% of the patients, but reflux is not as frequent as after myotomy. At present medical treatment is only indicated temporarily prior to dilatation or surgery. Surgical treatment is recommended for patients with contemporary delayed gastric emptying, hiatal hernia, vigorous achalasia, epiphrenic diverticula and for children with achalasia. For the remaining patients both methods can be used but after 2-3 dilatations myotomy is recommended.

[The role of nitrogen oxide synthesis for relaxation of the internal anal sphincter]. / Betydningen af nitrogenoxidsyntese for relaksation af den interne anale sphincter.

The purpose of the present study was to examine the role of the L-arginine-nitric-oxide pathway in neurogenic relaxation of the internal anal sphincter. Muscle strips representing the internal anal sphincter were prepared from 17 adult opossums. The preparations were mounted in organ baths for recording of isometetric tension. N omega-nitro-L-arginine, an agent known to inhibit the L-arginine-nitric oxide pathway, concentration-dependently reduced relaxation induced by transmural field stimulation. At the highest concentration of N omega-nitro-L-arginine (10(-4) M), no relaxation was evoked at any frequency tested (0.5-40 Hz). The inhibitory response to exogenous VIP was unaffected by N omega-nitro-L-arginine pretreatment, indicating that VIP relaxation does not utilize the L-argining-nitric oxide pathway. It is concluded that the non-adrenergic, non-cholinergic innervation of the internal anal sphincter involves an inhibitory substance generated from the L-arginine--No pathway. Whether this substance is nitric oxide or a related nitroso compound remains to be settled.

Clinical and proctoscopic evaluation of topical formalin application in the treatment of chronic radiation proctitis.

BACKGROUND AND AIMS: Chronic radiation proctitis is a disease associated with radiotherapy of cancer in the pelvic region. The main symptom is rectal bleeding. Several treatment modalities have been attempted, but few have demonstrated satisfactory effects. We present our experience with formalin applied locally to the rectal mucosa in the treatment of chronic radiation proctitis. Furthermore, we assess possible complications, the gravest suggested being cancer. Previous studies on the subject have reported good results, but often with a somewhat vaguely defined follow-up. Our evaluation of the treatment was based on both subjective symptoms and proctoscopic findings. MATERIAL AND METHODS: A small study (N = 11) was conducted retrospectively. All patients treated for chronic radiation proctitis with formalin in our clinic were identified, and data concerning effect and complications were collected by studying the patients' records, with a questionnaire and a follow-up interview and proctoscopy. RESULTS: The study showed a marked decrease in bleeding and objective signs of proctitis in all patients. Complete cessation of bleeding was achieved in five patients. Possible complications to the treatment detected in our study were the following: anorectal pain, tenesmus, incontinence, diarrhea, and mucous rectal discharge. No signs of neoplasia were found. CONCLUSIONS: The formalin treatment had a very good effect on chronic radiation proctitis. Possible complications were detected. Except in the case of anorectal pain, these are all of a questionable nature and can possibly be attributed to chronic radiation proctitis itself rather than the formalin treatment. Further study is warranted to confirm long-term effects of the formalin and to exclude possible complications, especially secondary anorectal cancer.

Drought in Africa caused delayed arrival of European songbirds.

Despite an overall advancement in breeding area arrival, one of the latest spring arrivals in northwest Europe since 1950 of several trans-Saharan songbird species occurred in 2011. Year-round tracking of red-backed shrikes and thrush nightingales revealed that the cause of the delay was a prolongation of stopover time during spring migration at the Horn of Africa, which was affected by extreme drought. Our results help to establish a direct link at the individual level between changes in local climate during migration and arrival and breeding condition in Europe thousands of kilometers further north.

Diagnostic value of self-reported symptoms in Danish outpatients referred with symptoms consistent with colorectal cancer.

OBJECTIVE: To assess the association between self-reported symptoms and a diagnosis of colorectal cancer (CRC) in symptomatic outpatients without CRC risk factors, defined by a Danish expert group. METHOD: A cross-sectional study of patients aged 40 years and older referred by general practitioners to two Danish surgical outpatient clinics for symptoms consistent with CRC during a 16-month period. CRC was diagnosed at endoscopy and through follow up. Before their first appointment, participants completed a questionnaire about symptoms. RESULTS: The study included 2172 patients. Of these, 122 were diagnosed with CRC (5.6%). Median age was 61 years (range: 40-97) and 44.0% were men. All symptoms had high (93.4-96.8%) negative predictive values for CRC. The highest positive predictive values (PPV) were found for dark rectal bleeding (PPV: 20.6%) and CRC was diagnosed in a first-degree relative over the age of 50 years (PPV: 11.2%). At multiple logistic regression analysis dark rectal blood was the most important predictor of CRC (OR: 7.4). Other predictors were age 60 years or older (OR: 3.0), change in frequency of bowel movements (OR: 2.5), CRC diagnosed in a first-degree relative over the age of 50 years (OR: 2.6), male gender (OR: 2.2) and mono-symptomatic fresh rectal blood (OR: 1.7). CONCLUSION: No self-reported symptoms presented by outpatients without CRC risk factors can be used accurately to identify patients with CRC with certainty. For clinical purposes self-reported symptoms seems thus not to be a useful accurate tool to distinguish between symptomatic outpatients with and without CRC.

Surveillance of surgical training by detailed electronic registration of logical components.

OBJECTIVE: To obtain detailed information about the degree of surgical trainee supervision and delegation of procedures in a subspecialised department. DESIGN: Operative procedures and their logical components were recorded in a database constructed in Microsoft Access. Information about operating surgeon and assistants and their grade was registered prospectively over 12 months. SUBJECTS AND METHODS: A total of 1250 intermediate or major procedures were performed by eight consultants, one staff specialist, four senior registrars, three specialist registrars, and five registrars. MAIN MEASURE: Number of components performed by surgeons in each grade and the degree of supervision and delegation. RESULTS: Eight hundred and eighty five of the operations were elective, while 365 were done as emergency procedures. Emergency procedures were far more often done by surgeons in training than by a staff surgeon, while the opposite was true for elective operations. Out of 323 elective operations done by surgeons in training, 189 were done under supervision (58.5%), while 119 out of 276 emergency operations done by surgeons in training were supervised (43.1%; p=0.0002). One hundred and twenty eight of 638 (20%) open abdominal operations were done by the most junior surgeons, and yet they closed 36% of all abdominal wounds. Although the most junior surgeons only served as operating surgeons in 39 of 334 bowel operations (12%), they constructed 24% of all stomas, and 20% of all anastomoses. Registrars and specialist registrars never constructed stomas or anastomoses without supervision. CONCLUSION: Detailed information about individual and general training and supervision was achieved by a simple registration. Significant additional information was obtained about the extent of delegation of components compared with standard registration of operative procedures.

The role of the L-arginine-nitric oxide pathway for peristalsis in the opossum oesophageal body.

BACKGROUND: The aim of the study was to determine the effect of NG-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide (NO) synthesis, on primary peristalsis in the oesophageal body. METHODS: Peristalsis was induced by pharyngeal stroking in 14 lightly anaesthetized opossums. Oesophageal pressures were monitored with a four-channel, perfused catheter assembly and registered with external transducers 1, 4, 7, and 10 cm proximal to the oesophagogastric junction. Propagation time was the time taken for a contraction to travel between two recording sites and was determined in the proximal, middle, and distal parts of the oesophagus (propagation time between 10 and 7 cm, 7 and 4 cm, and 4 and 1 cm recording sites, respectively). RESULTS: L-NNA (10(-7)-10(-5) mol/kg) dose-dependently reduced propagation time of the contraction in the distal oesophagus from 1.13 +/- 0.24 sec to 0.27 +/- 0.19 sec, whereas propagation in the proximal and middle parts of the oesophagus was unaffected. NG-nitro-D-arginine (D-NNA; 10(-5) mol/kg) had no influence on propagation time. In animals treated with L-NNA (10(-5) mol/kg) atropine (50 micrograms/kg) had no influence on propagation time in any part of the oesophagus. L-Arginine (10(-4) mol/kg) had no influence on the propagation time in animals treated with L-NNA (10(-5) mol/kg) and atropine (50 micrograms/kg). Neither D-NNA (10(-5) mol/kg) nor L-NNA (10(-7)-10(-5) mol/kg) influenced the amplitude of the contractions at any of the recording sites. In animals given L-NNA (10(-5) mol/kg) atropine (50 micrograms/kg) reduced the amplitude of the contraction significantly only at the distal recording site (1-cm recording site) from 62.0 +/- 4.9 mmHg to 34.5 +/- 5.3 mmHg. L-Arginine (10(-4) mol/kg) had no effect on the amplitude of contractions. CONCLUSION: The L-arginine-NO pathway plays a role in the control of primary peristalsic contractions of the oesophagus.