[Gastroentérologie Clinique et Biologique: a century's history of digestive system diseases]. / Gastroentérologie Clinique et Biologique: un siècle d'histoire des maladies de l'appareil digestif.

The journal Gastroentérologie clinique et biologique succeded to Archives des maladies de l'appareil digestif published since 1907 and is one of the world's oldest journals in gastroenterology. Gastroentérologie Clinique et Biologique was created as the discipline was emerging, benefiting from new techniques such as nasogastric intubation, coprologic examinations, the first images from gastrointestinal radiology, as well as the enormous progress made in gastrointestinal surgery. The journal was founded by Albert Mathieu, a remarkable chef d'école at Paris's Saint-Antoine Hospital. The journal showed rapid success, becoming the official organ of several learned societies, in particular the French National Society of Gastroenterology (Société nationale française de gastroentérologie [SNFGE]). Thoroughly updated in the 1970s, Gastroentérologie clinique et biologique has never ceased to evolve, adapting to technical and scientific upheavals, the globalization of knowledge, and the domination of the English language.

Intrarectal injection of glycerol induces hypersensitivity to rectal distension in healthy subjects without modifying rectal compliance.

BACKGROUND: Rectal sensory thresholds are lowered in patients with irritable bowel syndrome (IBS), reflecting visceral hyperlagesia, which might be related to subclinical inflammation. AIM: To evaluate the effects of an intraluminal injection of glycerol, a mucosal irritant, on rectal tone and perception of distension in 12 healthy subjects. METHODS: Rectal tone was evaluated with a barostat. First sensation, need to defecate and pain thresholds were evaluated during isobaric phasic distensions, before and 20 and 120 min after injection of 10 ml glycerol in the rectum. RESULTS: Baseline bag volume (97.9 +/- 56.2 ml) significantly decreased 20 min (49.7 +/- 42.2 ml; P= 0.026) and 120 min (66.5 +/- 38.3 ml; P= 0.050) after injection of glycerol, indicating its hypertonic effect. The pressure defining sensory thresholds was decreased significantly 20 min after glycerol injection: first sensation, 14.6 +/- 2.9 versus 18.3 +/- 7.2 mm Hg (P = 0.01); need to defecate, 19.6 +/- 3.7 versus 26.0 +/- 6.9 mm Hg; pain, 23.8 +/- 4.5 versus 35.6 +/- 9.5 mm Hg (P = 0.001). This effect was maintained for 120 min after injection of glycerol. Slopes of the compliance curves did not differ before and after injection of glycerol. CONCLUSIONS: Intraluminal injection of glycerol significantly increases rectal tone and sensitizes healthy volunteers to rectal distension, since they show significantly lower thresholds after glycerol. This could constitute a model of visceral hypersensitivity in healthy volunteers.

Role of EUS in the management of pancreatic and ampullary carcinoma: a prospective study assessing resectability and prognosis.

BACKGROUND: Endoscopic ultrasonography (EUS) is highly accurate for the staging of tumors, but its role in the management of periampullary carcinoma is still being defined. METHODS: Seventy-nine patients with pancreatic (n = 73) or ampullary (n = 6) carcinoma underwent prospective evaluation by means of assessment of resectability and survival according to the following three-step staging algorithm: (1) ultrasonography and computed tomography; (2) if tumor appears resectable, EUS; (3) if criteria of resectability are found at EUS, laparotomy for curative resection. RESULTS: The first step of the algorithm helped predict unresectability of tumors and need for palliative treatment for 36 patients. Among the other 43 patients EUS revealed signs of unresectability in 20 additional patients who then underwent palliative surgical or medical treatment (median survival time 7 to 8 months). Twenty-three carcinomas were considered resectable according to EUS findings: Palliative surgery was performed in 9 cases (survival time 6 months), and 14 tumors could be resected in a curative way with a median survival period of 15 (pancreatic) to 16 months (ampullary). In evaluation of resectability, EUS had a 50% sensitivity (positive examination), 100% specificity, 100% positive predictive value, 61% negative predictive value, and 72% accuracy. CONCLUSIONS: EUS is accurate for evaluating resectability of ampullary and pancreatic cancer. EUS staging can prevent unnecessary surgery, and the findings correlate well with prognosis. The management of ampullary and pancreatic cancer could be improved with EUS.

Role of vasoactive intestinal polypeptide in the adaptation of intestinal smooth muscle cells to mechanical distension.

Distension of the small intestine can play a role in the pathogenesis of various functional intestinal disorders. This study determined the role of vasoactive intestinal polypeptide (VIP) in the adaptative response of intestinal smooth muscle to acute and chronic distension of the ileum in vivo. Several in vitro experiments were performed to identify the mechanism of receptor regulation. Distension was applied by a balloon inflated with air in the ileum either during a single episode in anesthetized or repeatedly in conscious guinea pigs. Then, muscle cells were isolated by enzymatic digestion from the distended and nondistended adjacent ileal segments. In addition, in vitro experiments were performed on freshly dispersed cells for determination of mechanisms. Control cells maximally relaxed (Cmax) at 1 microM VIP (EC50 = 50 pM) and 100 microM isoproterenol (EC50 = 7 nM). Both acute and chronic distensions triggered a right-ward shift of the concentration-response curves for VIP (Cmax = 100 microM, EC50 = 10 nM). A desensitization of the relaxing effect of VIP receptors was also observed when cells were preincubated for 30 min in vitro with VIP. By contrast, the relaxing effect of isoproterenol was affected neither by in vivo distension nor by in vitro incubation with isoproterenol. Desensitization of VIP receptors was prevented by in vitro incubation of cells with VIP plus a VIP antagonist [(D-P-Cl-Phe6,Leu17)VIP] and by intraluminal perfusion of the VIP antagonist during acute distention in vivo. Moreover, desensitization of VIP receptors did not occur after 30 min preincubation with either forskolin or 8-Bromo-cyclic AMP. These results indicate that mechanical distension of the ileum induces a homologous desensitization of VIP receptors on circular smooth muscle cells, which requires the occupation of its receptors by VIP.

Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations.

Over the last decade, the role of visceral sensitivity has been largely recognized in the pathophysiology of functional digestive disorders, particularly in the irritable bowel syndrome. These studies have highlighted the role of afferent pathways arising from the gut as a possible target for new treatments intended to relieve pain or modify altered reflexes present in such patients. These pharmacological targets have been identified mainly by studies on animal models of visceral hyperalgesia of various origins including local inflammation. Locally, several mediators are of paramount importance for sensitization of nerve endings: 5-hydroxytryptamine, bradykinin, tachykinins, calcitonin gene-related peptide, and neurotrophins. Selective antagonists to various subtypes of their receptors are currently available and have been shown to be active in these animal models. Other substances, such as somatostatin, opiold peptides, cholecystokinin, oxytocin, and adenosine, modulate the transmission of nociceptive inputs from the gut to the brain and are of clinical interest. This article reviews the current understanding of these mediators. Although these agents seem to be promising tools for the treatment of visceral hyperalgesia and its consequences (abdominal pain and disturbed reflexes), their clinical efficacy remains to be shown. A better understanding of the nature and the location of the defect in the sensory pathways may permit the selection of subgroups of patients for treatment according to the pharmacological properties of these new therapeutic agents.

The calcitonin gene-related peptide activates both cAMP and NO pathways to induce relaxation of circular smooth muscle cells of guinea-pig ileum.

The direct effects and the intracellular pathways of rCGRP were investigated on smooth muscle cells (SMC) isolated by enzymatic digestion from the circular and longitudinal layers of guinea-pig ileum. In circular SMC, rCGRP inhibited CCK8-induced contraction in a concentration-dependent manner (Cmax = 100 microM and EC50 = 0.7 +/- 0.4 nM). Preincubation of SMC with 1 microM Rp-cAMPs, a cAMP antagonist, abolished the relaxing effect of rCGRP; moreover, preincubation of SMC with 100 microM L-NAME, an inhibitor of NOS, inhibited the relaxing effect of rCGRP, hCGRP(8-37), a selective antagonist of rCGRP receptors, inhibited the rCGRP-induced relaxation in a concentration dependent manner whereas the vasoactive intestinal polypeptide (VIP) antagonist had no significant effect. In longitudinal SMC, rCGRP-induced relaxation was abolished by Rp-cAMPs, whereas L-NAME had no effect. In conclusion, rCGRP triggers different intracellular pathways to induce relaxation of circular or longitudinal intestinal SMC; cAMP is involved in cells from both layers while nitric oxide (NO) is involved only in relaxation of circular SMC.

VIP-induced relaxation of guinea-pig intestinal smooth muscle cells: sequential involvement of cyclic AMP and nitric oxide.

1. A possible interaction between cyclic AMP and nitric oxide (NO) in mediating the relaxant effect of vasoactive intestinal polypeptide (VIP) on intestinal smooth muscle cells has been investigated. The effects of the inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME), have been studied on VIP-, forskolin-, and 8 bromo-cyclic AMP- induced relaxation of cells, dispersed by enzymatic digestion of muscle strips from the circular layer of guinea-pig ileum. 2. VIP alone did not modify the length of isolated muscle cells. By contrast, when the cells were contracted by cholecystokinin octapeptide, CCK8 (10 nM), VIP inhibited this contraction, inducing a concentration-dependent relaxation of the cells. Maximal relaxation was induced by 1 microM VIP (EC50 = 408.2 +/- 16.7 pM). 3. N-ethylmaleimide, inhibitors of adenylate cyclase or somatostatin, abolished the relaxing effect of VIP. (R)-p-cAMPs, an antagonist of cyclic AMP on protein kinase A also inhibited the VIP-induced relaxation by 92.1 +/- 6.3%. Inhibitors of nitric oxide synthase (NOS), L-NAME and L-NMMA, partially inhibited VIP-induced relaxation. The effect of L-NAME was reversed by L-arginine but not by D-arginine. 4. (R)-p-cAMPS and L-NAME also inhibited the cell relaxation induced either by forskolin which directly stimulates adenylate cyclase activity or 8-bromo-cyclic AMP, an analogue of cyclic AMP. 5. When cells were incubated for 30 min with dexamethasone 10 microM, a glucocorticoid known to decrease the synthesis of iNOS, the relaxing effect of a maximal concentration of VIP was decreased by 52 +/- 4% and L-NMMA had no further effect on this residual VIP-induced relaxation. Milrinone, a phosphodiesterase type III inhibitor, potentiated the relaxant effect of VIP. 6. These data demonstrate that the intracellular pathway mediating the relaxant effect of VIP in intestinal smooth muscle cells includes the sequential activation of adenylate cyclase, protein kinase A, activation of NOS and finally production of NO and cyclic GMP. NO could in turn regulate the cyclic AMP-dependent pathway of cell relaxation.

[Specific respiratory manifestations associated with hemorrhagic rectocolitis. Analysis of a case and review of the literature]. / Manifestations respiratoires spécifiques associées à la rectocolite hémorragique. Analyse d'un cas et revue de la littérature.

Respiratory impairments occurring as systemic manifestations of ulcerative colitis are often misinterpreted. We report a case of chronic productive bronchitis associated with ulcerative colitis; symptoms appeared after colectomy. Clinical features distinguished it from common chronic bronchitis: it occurred in a woman without respiratory disease or smoking history, a chronic productive cough without bronchiectasis, negative infectious investigations, severe endoscopic and histologic lesions, and above all remarkable steroid efficacy. Systematic research and early treatment of these manifestations avoids aggravating pulmonary disease, especially secondary bronchiectasis. Though less frequent, other respiratory manifestations of ulcerative colitis have been described, such as asphyxiating tracheal stenosis, pneumonia or interstitial pulmonary diseases, pleurisy or pleuro-pericarditis.

[Efficacy and tolerance of praziquantel (Biltricide) in the treatment of distomatosis caused by Fasciola hepatica]. / Efficacité et tolérance du praziquantel (Biltricide) dans le traitement de la distomatose à Fasciola hepatica.

OBJECTIVES: Due to the side-effects of dehydroemetine, we have chosen praziquantel, a broad-spectrum antihelmintic, as a treatment for distomatosis secondary to Fasciola hepatica in humans. The aim of this retrospective study was to evaluate the efficacy and tolerance to praziquantel in patients with this disease. METHODS: Twenty-five patients (12 men) with a definite diagnosis of distomatosis and no previous treatment were followed-up between 8 months and 3 years (> 18 months in 76% of cases). The follow-up was based on clinical, biochemical and serological criteria. All patients received praziquantel (75 mg/kg/day orally) for 5 days. Treatment was started after endoscopic or surgical removal of parasites locolized in the biliary tract, in two patients. A similar therapeutic course was administered twice in four patients with persistent clinical symptoms, hypereosinophilia or arch 2 on immunoelectrophoresis. RESULTS: Cumulative rates of patients with normalized eosinophilia and seronegativation at 6, 9 and 12 months were 55, 65, 75% and 55, 70, 100%, respectively. Complete recovery occurred in 18 patients (72%) whereas hypereosinophilia persisted for more than one year in 5 patients. No side-effects, except transient nausea in a few cases, were observed. CONCLUSION: Since praziquantel seems to be both effective and well tolerated in a large proportion of patients, this drug can be recommended as a first choice for distomatosis due to Fasciola hepatica in human.

Endoscopic ultrasonography in chronic pancreatitis: a comparative prospective study with conventional ultrasonography, computed tomography, and ERCP.

The usefulness and accuracy rate of endoscopic ultrasonography (EUS) in the diagnosis of chronic pancreatitis (CP) were prospectively evaluated in 81 patients with suspected pancreatic disease. All underwent EUS, abdominal ultrasonography (AUS), and computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) was performed in 55 of the cases. The diagnosis of CP was established in 44 patients (CP group) including 24 with a calcified form. No pancreatic disease was observed in 18 patients (control group), and 19 patients had a pancreatic tumor. In the CP group AUS was less accurate than EUS in visualizing the pancreas, performances of CT scan being identical to EUS in this respect. A good correlation was observed between EUS and ERCP for visualization and measurement of the Wirsung duct. The most significant changes observed by EUS in the CP group were dilatation of the main pancreatic duct, heterogeneous echogenicity of the pancreatic parenchyma, and cysts < 20 mm in size even in noncalcified CP or with normal pancreatograms. Sensitivity of EUS for diagnosis of CP was 88% (AUS, 58%; ERCP, 74%; CT scan, 75%), the specificity being 100% for ERCP and EUS, 95% for CT scan, and 75% for AUS. The good performances of EUS allow early diagnosis of CP in symptomatic patients since heterogeneous echogenicity of the pancreatic parenchyma seems to be almost specifically associated with the disease.

Galanin contracts and relaxes guinea pig and canine intestinal smooth muscle cells through distinct receptors.

BACKGROUND/AIMS: Galanin induces a contraction or a relaxation of digestive smooth muscle. Receptors mediating these effects have not been pharmacologically characterized. The aim of the study was to evaluate properties of two specific galanin antagonists M15 and M35 on galanin effects on muscle cells. METHODS: Isolated muscle cells were obtained separately from circular and longitudinal layers of guinea pig and dog ileums. Contraction was expressed as percentage decrease in cell length from control. RESULTS: Galanin induced a contraction of cells from guinea pig circular layer (50% effective concentration [EC50], 80 pmol/L) and dog longitudinal layer (EC50, 100 pmol/L). The antagonists inhibited galanin-induced contraction. The most potent was M15 (50% inhibitory concentration [IC50], 80 pmol/L in guinea pig; 90 pmol/L in dog) which was > M35 (IC50, 4 nmol/L in guinea pig; 1 nmol/L in dog). In dog circular layer, galanin inhibited cholecystokinin-induced contraction by relaxing the cells (EC50, 3 pmol/L). The antagonists inhibited this relaxation. The most potent was M35 (IC50, 60 pmol/L) which was > M15 (IC50, 900 pmol/L). CONCLUSIONS: Galanin antagonists M15 and M35 inhibit the contraction and the relaxation induced by galanin with different potency, suggesting the presence of distinct galanin receptors in gastrointestinal tract that each mediates a specific effect.

Parathyroid hormone (PTH) and PTH-related peptide induce relaxation of smooth muscle cells from guinea pig ileum: interaction with vasoactive intestinal peptide receptors.

PTH-related peptide (PTHrP), which shares 8 of 13 NH2-terminal residues with PTH, causes similar biological effects and interacts with the same receptor as PTH. In the gastrointestinal tract, human PTH and PTHrP-(1-34) relax rat fundic strips. However, the level of their action and the receptor involved in this effect are unknown. The aims of this study were 1) to determine the effects of human PTH-(1-34), human PTHrP-(1-34), -(1-16), and -(7-34) and vasoactive intestinal peptide (VIP) on circular isolated smooth muscle cells from guinea pig ileum; 2) to study the intracellular pathways involved in these effects; and 3) and to characterize the receptors involved by using specific antagonists. Smooth muscle cells were dispersed by enzymatic digestion. Contraction was assessed by measuring the length of 50 cells and expressed as the percent decrease in cell length from the control value. The relaxing effects of PTH, PTHrP and analogs, VIP, or antagonists were expressed as a percentage of the maximal effect observed in their absence. VIP, PTH-(1-34), and PTHrP-(1-34), -(1-16), and -(7-34) had no effect by themselves on these cells. However, when cells were contracted by the sulfated C-terminal octapeptide of cholecystokinin (10 nM), VIP, PTH-(1-34), and PTHrP(1-34) inhibited the sulfated C-terminal octapeptide of cholecystokinin-induced contraction in a concentration-dependent manner, whereas PTHrP-(1-16) and -(7-34) had no effect. The EC50 values of VIP, PTH-(1-34), and PTH-(1-34), and PTHrP-(1-34) were 7 nM, 20 pM, and 20 pM, respectively. The VIP antagonist ([D-P-Cl-Phe6,Leu17]VIP) inhibited VIP-, PTH-(1-34)-, and PTHrP(1-34)-induced relaxation, with IC50 values of 20, 500, and 400 pM, respectively. Likewise, the PTH/PTHrP antagonist [Tyr34-bovine PTH-(7-34)NH2] inhibited PTH-(1-34)-, PTHrP(1-34)-, and VIP-induced relaxation, with IC50 values of 1, 1, and 90 pM, respectively. Preincubation of cells with somatostatin, N-ethylmaleimide, and (R)-p-cyclic adenosine-3',5'-monophosphothioate inhibited the PTH-(1-34), PTHrP(1-34)-, and VIP-induced relaxation. In conclusion, human PTH and PTHrP induce a relaxation of intestinal smooth muscle by a direct myogenic effect. This effect requires the 1-34 amino acid sequence and is mediated by the activation of adenylate cyclase and protein kinase-A. Interactions among PTH, PTHrP, and VIP indicate that they may cross-react with their respective receptors.

Nd:YAG laser in treatment of rectal cancer. Are there features predicting a curative result?

In the present study we report the results of Nd:YAG laser treatment in 36 patients with rectal carcinoma in whom negative biopsies were obtained at the end of the treatment. The laser (100-W maximal power output) was applied through a flexible endoscope during 20- to 40-min sessions repeated every three days until the lesion was destroyed completely. Follow-up examinations, including endoscopy with biopsies, liver and endorectal ultrasonography and chest x-ray were performed every three months during the first year and thereafter once a year. Between 1980 and 1991, 272 patients were treated. All were unfit for surgery because of metastasis (78), recurrence after an other procedure (54), associated conditions, or old age (140). No circumferential tumors of any size were obliterated, but among the 139 patients presenting with a noncircumferential lesion less than 7 cm in diameter, negative biopsies were obtained after laser treatment in 36 patients (26%). Of these 36 patients, eight had been treated previously by surgery (5) or radiotherapy (3). Mean follow-up is 37 months (range 12-71). Recurrences were observed in four cases. Seven patients died during the study but only one death was related to the cancer (pelvic extension 19 months after treatment). Endorectal ultrasonography was performed prior to treatment in 15 patients and showed no invasion of the rectal wall deeper than the submucosa. After treatment, endorectal ultrasonography in 22 patients showed significant changes corresponding to cicatricial pattern in 60% of controlled patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Galanin induces opposite effects via different intracellular pathways in smooth muscle cells from dog colon.

Smooth muscle cells isolated by enzymatic digestion were used to determine the direct effects of galanin on circular and longitudinal muscle layers from dog proximal colon and to investigate the intracellular pathways involved in these effects. Effects of galanin were compared to those observed with other contracting [cholecystokinin octapeptide (CCK8)] and relaxing [vasoactive intestinal peptide (VIP)] agents. In longitudinal cells, galanin and CCK8 induced a contraction that was maximal at 1 nM galanin and 1 nM CCK8 and was 23.9 +/- 4.5% and 23.4 +/- 3.4%, respectively, of the length of resting cells. Incubation of cells in Ca(2+)-free medium or in the presence of nifedipine caused an inhibition of galanin-induced contraction whereas it had no effect on the contraction induced by CCK8. Vasoactive intestinal peptide, forskolin, and 8 bromo cAMP inhibited CCK-induced contraction but failed to inhibit contraction induced by galanin. The contraction induced by galanin was abolished; the CCK-induced contraction was unchanged by pertussis toxin. In circular cells, CCK8 induced a contraction that was maximal at 10 nM and was 24.2 +/- 2.6%. Galanin had no effect by itself. When cells were preincubated (1 min) with galanin (10 fM-1 microM), the CCK8-induced contraction was inhibited, with a maximal effect at 10 nM galanin. Likewise, VIP inhibited the CCK8-induced contraction with a maximal effect at 1 microM. Preincubation of cells with somatostatin, N-ethylmaleimide, and (R)-p-cAMPS inhibited galanin- and VIP-induced relaxation. In conclusion, galanin induces a contraction of longitudinal smooth muscle cells that is dependent on an influx of extracellular calcium and an activation of pertussis toxin G-protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet-activating factor (PAF) induces a contraction of isolated smooth muscle cells from guinea pig ileum: intracellular pathway involved.

This study was designed to evaluate the effect of platelet-activating factor (PAF) on isolated smooth muscle cells from guinea pig ileum circular layer, to characterize the PAF receptors involved in this effect and to determine the intracellular pathways triggered by PAF. Cells dispersed by enzymatic digestion were incubated for 30 sec in the presence of PAF and fixed by glutaraldehyde. When inhibitors or antagonists were tested, cells were preincubated with them for 1 min. Then PAF was added for 30 sec, and the cells were fixed. Contraction was assessed by measuring the length of 50 cells and was expressed as the percentage decrease in cell length from controls. The relaxing effect of inhibitors was expressed as the percentage of the maximal contraction observed in their absence. PAF induced a cell contraction in a concentration-dependent manner. Maximal contraction (24.2 +/- 4.2%) was obtained for a PAF concentration of 10 nM (EC50 = 10 pM). PAF-induced contraction was inhibited by the PAF receptor antagonists BN52021, L659.989 and SR27417. Contraction induced by 10 nM PAF was inhibited when cells were incubated in Ca(++)-free medium with or without 2 mM EGTA or in a 1 mM Ca++ medium to which 100 nM nifedipine was added. When cells were preincubated with concentrations ranging from 0.01 pM to 10 microM of relaxing agents (vasoactive intestinal polypeptide, forskolin, 8 Bromo cAMP) known to increase the intracellular level of cAMP, PAF-induced contraction was inhibited. Moreover, when cells were preincubated with pertussis toxin (200 ng/ml) or cholera toxin (8.4 ng/ml), contraction induced by PAF was also inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracellular pathways triggered by galanin to induce contraction of pig ileum smooth muscle cells.

1. In order to determine the intracellular mechanisms by which galanin induces contraction of isolated smooth muscle cells from pig ileum, we examined the effects of external Ca2+, relaxing agents, pertussis toxin and forskolin on the galanin-induced contraction and compared these effects to those observed on the cholecystokinin derivative CCK8-induced contraction. 2. Galanin induced a concentration-dependent cell contraction. The maximal contraction (24.5 +/- 2.1% of the length of resting cells) was observed at 1 nM of galanin. When cells were incubated in the simultaneous presence of concentrations of galanin (10 fM) and CCK8 (1 pM) which were ineffective alone, or galanin (10 fM) and acetylcholine (100 pM), a synergistic action was observed corresponding to a submaximal contraction. 3. Incubation of cells in Ca(2+)-free medium caused a significant decrease in galanin- but not in CCK-induced contraction. Nifedipine, a Ca2+ channel blocker, provoked a concentration-dependent inhibition of galanin-induced contraction while it had no effect on the contraction induced by CCK8. 4. Vasoactive intestinal polypeptide (VIP) and isoprenaline, known to induce cell relaxation through an increase in intracellular cAMP level, inhibited CCK-induced cell contraction at concentrations ranging from 1 pM to 1 microM but failed to inhibit cell contraction induced by galanin. 5. When cells were pre-incubated for 3 h in the presence of 200 ng/ml of pertussis toxin, the contraction induced by galanin was abolished while the CCK-induced contraction remained unchanged. On the contrary, 10 microM forskolin abolished the contraction induced by 10 nM CCK but had no effect on galanin-induced contraction. 6. These results indicate that galanin induces a concentration-dependent contraction of pig ileum smooth muscle by a direct myogenic effect. This effect of galanin involves the activation of a pertussis toxin-sensitive G protein, which results in an influx of Ca2+ into the cell. This intracellular pathway is insensitive to the relaxing effect of cAMP.

Differences between jejunal myoelectric activity after a meal and during phase 2 of migrating motor complexes in healthy humans.

Using an intraluminal probe with six pairs of annular electrodes, the myoelectric activity of the proximal jejunum was recorded during 48-hr sessions in 16 healthy volunteers receiving evening and noon meals (1000 kcal) and breakfast (400 kcal). In 10 subjects receiving no drug, the characteristics of the migrating motor complexes (period, duration of each phase, velocity of propagation of phase 3, duration of the postprandial disruption) varied markedly between subjects but were relatively constant from the first to the second day of recording. Single spike bursts propagated at a rate of 2-5 cm/sec, clusters of 3-10 spike bursts propagated at a rate of 0.5-1 cm/sec, and similar clusters recurring repetitively each 1.5-2 min were observed after the meals and very rarely in the fasted state during phase 2 of nocturnal migrating motor complexes. In six subjects, oral administration of codeine (50 mg) 1 hr before a meal induced migrating motor complexes in the postprandial state, with characteristics similar to that observed in the fasted state except a longer duration of phase 2. Single spike bursts and isolated and repetitive clusters of spike bursts were observed during phase 2 of the codeine-induced migrating motor complexes and after meals preceded by placebo, but very rarely during the phase 2 of nocturnal (fasted state) migrating motor complexes. It is concluded that the patterns of jejunal contractions consisting of propagated single spike bursts and isolated or repetitive spike bursts characterize the postprandial state in healthy humans and are dependent upon digesta flow.

[Incidence, treatment and prognosis of cancer of the pancreas in Haute-Garonne (1982-1986)]. / Incidence, traitement et pronostic du cancer du pancréas en Haute-Garonne (1982-1986).

The characteristics of incident cases of pancreatic carcinoma found in the area of Haute-Garonne (France), as determined by the Digestive Cancer Registry, are reported. Two hundred and forty-six new cases were collected during a 5 year period in a population of 820,000 inhabitants. The annual standardized incidence rate per 100,000 inhabitants was 4.7 for men and 2.6 for women, respectively. This represents a low risk and corresponds to 7 percent of all intestinal tract tumors. The tumors were shown histologically to be adenocarcinoma in 85 percent of cases. The tumor was localized in the head of the gland in 64 percent of cases, while metastases were present at the time of diagnosis in 43 percent of cases. Ultrasonography was the initial investigation (44 percent of cases) and was performed well before endoscopic retrograde wirsungography (12.8 percent) and computed tomography (18 percent). Eighty-six percent of the patients were operated on. Curative surgery, however, was possible in only 12.5 percent of patients. The incidence of carcinoma remained stable during the observation period and no change was noticed with regard to housing conditions. During follow-up, 50 of 215 patients died within one month following the diagnosis (23 percent). Actuarial survival was 36 percent at 6 months, 17.4 percent at one year, and 3.6 percent at 3 years. These data were comparable to those observed in the Côte-d'Or and Calvados areas. These findings suggest that the French Digestive Tumor Registries should develop co-operative studies particularly in the analytic epidemiological fields.