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.

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.

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.

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.

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.

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.

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.

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.

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.

Relative effects of dihydropyridine L-type calcium channel antagonism on biliary, duodenal, and vascular tissues: an in vivo and in vitro analysis in Australian brush-tailed possum.

Nifedipine is used to treat sphincter of Oddi dysfunction. Its effects on the biliary system and duodenum in relation to its known vascular actions are unclear. Our aims were to determine the relative tissue sensitivities to dihydropyridine L-type calcium channel antagonism in the sphincter of Oddi, gallbladder, duodenum, and vasculature. For in vivo studies, 23 possums received nifedipine at three different doses with blood pressure and sphincter of Oddi manometry recordings. For in vitro studies, tissues from 28 possums were pretreated with nicardipine (10(-8)-10(-5) M) and cumulative concentrations of agonist were administered (carbachol, norepinephrine at 10(-9)-10(-5) M). In in vivo studies, blood pressure fell significantly at a lower dose than sphincter of Oddi motility. In in vitro studies, the sphincter of Oddi was more sensitive than arterial tissue, with the duodenum especially sensitive. In conclusion, in the possum we found that L-type channel antagonism in vivo was more potent to the vasculature than the sphincter of Oddi but this was not confirmed in vitro.

Excessive nodular hyperplasia of Brunner glands associated with gastric hypersecretion and lipomatous atrophy of the pancreas.

The case of a 34-year-old woman complaining of diarrhoea and abdominal pain is presented. Contrast radiography and endoscopy showed multiple polypoid tumours in the second part of the duodenum. Moreover, a severe fatty infiltration of the pancreas was shown by magnetic resonance and computed tomography scans. Due to pain, pancreatoduodenectomy (Whipple operation) was performed, and subsequent histopathologic examinations showed excessive Brunner gland hyperplasia of the duodenum and severe lipomatous atrophy of the pancreas. The occurrence of these two rare conditions in one patient has not been described previously, and it is conceivable that the lipomatous atrophy and exocrine insufficiency of the pancreas may have caused a compensatory stimulation of the submucosal structures of the duodenum.

Effects of transmural field stimulation in isolated smooth muscle of human rectum and internal anal sphincter.

Smooth muscle preparations from the circular muscle layer of the most distal rectum and the proximal and distal human internal anal sphincter (IAS) mounted in organ baths to record isometric tension developed spontaneous tension. Transmural electrical field stimulation (TMS) induced frequency- and impulse duration-dependent relaxations sensitive to tetrodotoxin in the stimulation range of 0.5-40 Hz and 0.04-0.6 ms. Poststimulus contractions were most frequent and prominent in rectal preparations. Maximal relaxations were comparable in the three locations and were achieved at 10 Hz and 0.4 ms. The frequency inducing half-maximal response was lower in rectal strips compared with IAS. Phentolamine (10-(6) M) enhanced relaxations and diminished off-contractions at 40 Hz in distal IAS. N omega-nitro-L-arginine (L-NNA) concentration dependently inhibited both relaxations and off-contractions (10 Hz, 0.4 ms). The pD2 values (-log EC50) of L-NNA were lower in rectal muscle compared with those in IAS. L-Arginine (10-(4) M) inhibited the blocking effect of L-NNA. In one-half of the preparations, L-NNA reversed the relaxations to duration contractions (15-40 Hz), which were inhibited by atropine in rectal preparations and by phentolamine in IAS. In conclusion, excitatory innervation of the IAS is alpha-adrenergic and cholinergic in the rectum. A product of the L-arginine-nitric oxide pathway mediates the TMS-induced inhibition of the muscle and is also involved in poststimulus contractions.

Transmitter interactions in rabbit internal anal sphincter.

The aim of the present study was to investigate the relative importance of the different putative nonadrenergic noncholinergic (NANC) mediators and their interplay with cholinergic nerves in the rabbit internal anal sphincter (IAS). IAS preparations were mounted in organ baths for recording of isometric tension. Transmural field stimulation (TMS; 5-s trains; supramaximal voltage, 140-160 V; 0.4-ms impulse duration) was applied every 2 min with frequencies varying from 0.2 to 32 Hz. TMS induced frequency-dependent relaxations that amounted to 89.3 +/- 2.2% (n = 7). N omega-nitro-L-arginine (L-NNA; 10(-7)-10(-4) M; 8 Hz) reduced relaxations and this effect was partially inhibited by preincubation with L-arginine (10(-4) M). The effect of L-NNA was attenuated by atropine preincubation. Apamin (10(-6) M) shifted the frequency-response curve to the right but left maximal relaxations in response to TMS unaffected. In the presence of L-NNA (10(-4) M) and atropine (10(-6) M), the action (area between the frequency-response curve with or without a substance) of apamin was more pronounced, but, despite the presence of both L-NNA and apamin, some relaxation still remained. The frequency-response curve (control) was significantly shifted to the right by carbachol (10(-6) M). Concentration-response experiments showed that the response to exogenous nitric oxide (NO; 10(-7)-10(-4) M) was unaffected by carbachol (10(-6) M) preincubation, whereas responses to vasoactive intestinal polypeptide (VIP) and ATP were significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

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 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.

Effects of transmural field stimulation in isolated muscle strips from rabbit sphincter of Oddi and duodenum.

The purpose of the study was to compare the effect of transmural field stimulation (TMS) on isolated smooth muscle strips from rabbit sphincter of Oddi (SO), duodenal circular layer (Dc) and duodenal longitudinal layer (D1). The strips were suspended in thermostatically controlled 5-ml organ baths containing Krebs solution constantly bubbled with 5% CO2 in O2. TMS was delivered through platinum electrodes (140 V, 0.4 ms, 5 s trains, 40 Hz). The TMS responses could be divided in two main responses: (1) contraction initiated after cessation of the stimulus train, preceded by an inhibitory phase during TMS ('off'); and (2) contraction initiated during TMS ('duration'). The 'duration' response was observed in one out of 20 strips in the SO and Dc compartments, whereas 11 D1 strips (55%) showed 'duration' responses (P < 0.001). Atropine (10(-6)) converted all 'duration' responses to an 'off' response preceded by an inhibitory phase during TMS and reduced the contractile amplitudes with 40-65%. L-NNA significantly increased the number of 'duration' responses in all types of muscle, and caused a 40% increase in D1 contractile amplitude. Inhibitory responses could not be removed by atropine, propranolol and phentolamine. The results suggest that the intrinsic innervation of SO and duodenal muscle consists of a mixture of excitatory, cholinergic and inhibitory NANC pathways. The latter may utilize, wholly or partly, NO or a related compound as transmitter. A relative dominance of excitatory, cholinergic responses was present in the D1 strips, whereas inhibitory responses were dominating in the SO and Dc strips.

The role of the L-arginine/nitric oxide pathway for relaxation of the human lower oesophageal sphincter.

Smooth muscle specimens were taken from the oesophagogastric junction (OGJ) in patients operated on for gastrointestinal malignancies not involving the OGJ. The smooth muscle bundles of the inner, circular layer of the OGJ were richly innervated by fine nerve fibres staining positively for NADPH diaphorase. The outer longitudinal layer had a markedly lower number of NADPH-diaphorase positive nerve fibres. When the preparations were suspended in organ baths for recording of isometric tension, they developed active tension. Transmural field stimulation (TMS) induced frequency-dependent relaxations, which were abolished by NG-nitro-L-arginine (L-NNA; 10(-4) M), and were often converted to atropine-sensitive contractions. The effect of L-NNA was concentration-dependent, and the concentration-response curve for L-NNA was shifted to the right by L-arginine pre-incubation. The enantiomer NG-nitro-D-arginine (10(-4) M) also showed inhibitory actions on the responses to TMS, but significantly less than L-NNA. Relaxant responses to vasoactive intestinal polypeptide (VIP), forskolin, and sodium nitroprusside were unaffected by L-NNA pre-incubation. Exposure to a 124 mM K+ solution resulted in a biphasic relaxation of the preparations. This relaxation was not seen in preparations treated with scorpion venom (20 micrograms ml-1) or L-NNA (10(-4) M). Instead, a contractile response to 124 mM K+ solution was found. The results suggest that NANC responses to electrical stimulation of nerves in the human OGJ are mediated by a product generated from L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the L-arginine/nitric oxide pathway in relaxation of isolated human penile cavernous tissue and circumflex veins.

In human penile corpus cavernosum strips, pre-contracted by noradrenaline, electrical stimulation of nerves evoked non-adrenergic, non-cholinergic (NANC) relaxant responses which could be inhibited by tetrodotoxin 10(-6) M, NG-nitro-L-arginine (L-NNA) 10(-7)-10(-4) M, and oxyhaemoglobin 10(-5) M, but not by methylene blue (MB) 10(-5) M. Acetylcholine-induced relaxations were also inhibited by L-NNA 10(-4) M and oxyhaemoglobin 10(-5) M, but were unaffected by pyrogallol 10(-4) M, MB 10(-5) M, and tetrodotoxin 10(-6) M. MB 5 x 10(-4)-10(-4) M significantly reduced the responses to both electrical stimulation and to acetylcholine. Nitric oxide (NO) 10(-7)-10(-4) M and sodium nitroprusside 10(-9)-10(-4) M caused concentration-dependent relaxations. The NO-induced relaxations were inhibited by oxyhaemoglobin 10(-5) M, and the concentration-response curve for sodium nitroprusside was shifted to the right by MB 10(-5) M. The response to sodium nitroprusside was unaffected by L-NNA 10(-4) M, oxyhaemoglobin 10(-5) M, and pyrogallol 10(-4) M. In circumflex veins, pre-contracted by noradrenaline, no NANC-mediated relaxation was found in response to electrical stimulation; acetylcholine caused endothelium-dependent relaxations, which were insensitive to L-NNA 10(-4) M and oxyhaemoglobin 10(-5) M. NO and sodium nitroprusside caused concentration-dependent relaxations; the concentration-response curves for NO and sodium nitroprusside were shifted to the right by oxyhaemoglobin 10(-5) M. Removal of the endothelium left the NO- and sodium nitroprusside-induced relaxations unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical properties of isolated smooth muscle from human rectum and internal anal sphincter.

The passive and active length-tension relations of the circular smooth muscle layer of the human distal rectum and the proximal and distal internal anal sphincter were investigated. Muscle strips were prepared and mounted in organ baths for recording of isometric tension. Resting lengths (LR) were measured, and the preparations were elongated stepwise. At each length, the corresponding values for passive tension, spontaneous active resting tension, and the submaximal active tension were recorded. Elongations of 200-380% of LR were possible before a sharp increase in passive tension occurred. None of the mean tension values measured at length for maximal active tension (LO) differed significantly among the three muscle types. All strips developed active resting tension. This tension was myogenic and contributed 10 +/- 3, 23 +/- 6, and 27 +/- 6% to the total active performance of rectal and proximal and distal sphincter preparations, respectively. Collagen constituted approximately 50% of smooth muscle biopsies, with highest contents in distal internal anal sphincter. This study provides an acceptable method for assessing the optimal experimental length by stretching the strips in an inactive state to 200% of LR, followed by individual adjustment of the passive tension to 5 mN/mm2 measured at 200% of LR.