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1. Abstract form for the Irish Journal of Medical Science v workshop on gastroduodenal pathology and Helicobacter pylori July 5th — 7th 1992 — Dublin, Ireland

Author

Logan, R. P. H., Gummett, P. A., Walker, M. M., Karim, Q. N., Baron, J. H., Misiewicz, J. J., Trieber, G., Walker, S., Klotz, U., Lozniewski, A., Weber, M., de Korwin, J. D., Floquet, J., Conroy, M. C., Burdin, J. C., Mannes, G. A., Bayerdörffer, E., Höchter, W., Weingart, J., Heldwein, W., Sommer, A., Müller-Lissner, S., Bomschein, W., Miehlke, S., Weinzierl, M., Ruckdeschel, G., von Wulffen, H., Köpcke, W., Stolte, M., Rune, S. J., Justesen, T., Hansen, J. M., Jensen, T. G., Eriksen, J., Thomsen, O. ø., Scheibel, J., Bonnevie, O., Bremmelgaard, A., Vilien, M., Knuhtsen, S., Elsborg, L., Hansen, J., Lauritsen, K., Wulff, H. R., Boixeda, D., Ballestero, S., Cantón, R., De Rafael, L., Martinm de Argila, C., Pozuelo, M. J., Sampedro, J., Baquero, F., Grigoriev, P. Ya., Isakov, V. A., Iakovenko, E. P., Hirschl, A. M., Brandstätter, G., Dragosics, B., Hentschel, E., Kundi, M., Rotter, M. L., Schütze, K., Taufer, M., Neri M, Susi D, Bovani I, Pindo R, Cuccurullo F., Coelho, L. G. V., Passos, M. C. F., Chausson, Y., Vieira, W. L. S., Castro, F. J., Franco, J. M. M., Fernandes, M. L. M., Castro, L. P., Jonas, C., De Koster, E., Van Gossum, M., Depierreux, M., Cheval, M., Deltenre, M., Schütz, E., Bethke, B., Lee, A., Hegedus, E., O’Rourke, J., Larsson, H., Sjöstedt, S., Veress, B., Nord, C. E., Sobala, G. M., George, R., Tompkins, D., Finlay, J., Manning, A., Sant, S., Xia, H. X., Daw, M., Gilvarry, J., Keane, C. T., O’Morain, C., Rubio, M. A., Hegarty, B., Blum, A. L., Sulser, E., Stadelmann, O., Munoz, N., Buiatti, E., Vivas, J., Oliver, W., Cano, E., Peraza, S., Castro, D., Sanchez, V., Andrade, O., Benz, M., Mendz, G. L., Hazell, S. L., Salmela, K. S., Roire, R. P., Hook-Nikanne, J., Kosunen, T. U., Salaspur, M., Luke, C. J., Reynolds, D. D. J., Penn, C. W., Bode, G., Mauch, F., Ditschuneit, H., Malfertheiner, P., Ferrero, Richard L., Agnes Labigne, Eaton, K. A., Krakowka, S., Mobley, H. L. T., Hu, Li-Tai, Foxall, P. A., Moran, A. P., Helander, I. M., Altman, C., Sobhani, I., Vissugaire, C., Migrant, M., Etienne, J. P., Sommi, P., Ricci, V., Fiocca, R., Cova, E., Figura, N., Romano, M., Ivey, K. J., Solcia, E., Ventura, U., Nilius, M., Schieffer, S., Hengels, K. J., Jablonowski, H., Strohmeyer, G., Cabrai, M. D., Barbosa, A. J. A., Lima Hr., G. F., Oliveira, C. A., Polak, J. M., Oderda, G., Villani, L., Altare, F., Morra, I., Miserendino, L., Ansaldi, N., Dixon, M. F., Wyatt, J. I., Axon, A. T. R., Beattie, S., Hamilton, H., Shabib, S., Cutz, E., Drumm, B., Sherman, P., Noach, L. A., Rolf, T., Bosma, N. B., Schwartz, M. P., Oosting, J., Rauws, E. A. J., Tytgat, G. N. J., Andrew, A., Nardone, G., d’Ormiento, F., Pontillo, M., Lobo, A. J., Uff, J. S., McNulty, C. N. M., Wilkinson, S. P., Suriani, R., Pallante, C., Ravizza, M., Galliano, D., Sallio, D., Malandrino, M., Oneglio, R., Colozza, M., Mazzucco, D., Gaia, E., Eidt, S., Vincent, P., Gottrand, F., Turck, D., Lecomte-Houcke, M., Leclerc, H., Bonvicini, F., Pretolani, S., Baraldini, M., Cilla, D., Baldinelli, S., Bazocchi, E., Acampora, P., Careddu, N., Brocchi, E., Gasbarrini, G., Joubert, M., Bazin, N., Thiaucourt, D., Protte, E., Gissler, C., Duprez, A., Merlin, P., Forestier, S., Labenz, J., Gyenes, E., Rühl, G. H., Börsch, G., Daskalopoulos, G., Carrick, J., Lian, R., Wagner, S., Bleck, J., Gebel, M., Bär, W., Manns, M., Lamouliatte, H., Bernard, P. H., Cayla, R., Vialette, G., Quinton, A., Mégraud, F., Lemaire, M., Quinten, A., De Mascarel, A., Webb, P., Forman, D., Knight, T., Wilson, A., Graves, S., Newell, D., Elder, J., Tonelli, E., Gatte, M. R. A., Ghironzi, G. C., Giulianelli, G., Bamford, K. B., Collins, J. S. A., Bickley, J., Johnston, B. T., Potts, S., Boston, V., Owen, R. J., Sloan, J., Basso, L., Lawlor, S., Clune, J., Szelényi, H., Stohmeyer, G., Macedo, G., Iglésias, I., Chaves, A. P., Loureiro, A., Katelaris, P. H., Seow, F., Lin, B., Napoli, J., Hones, D. B., Ngu, M. C., Akopyantz, Natalia S., Bukanov, Nikolay O., Westblom, T. Ulf, Berg, Douglas E., Nyst, J. F., Denis, P., Buset, M., De Reuck, M., Nielsen, H., Andersen, L. P., Birkholz, Sabine, Knipp, Ulrich, Nietzki, Claudia, Opferkuch, Wolfgang, Crabtree, J. E., Peichl, P., Lindly, I. J. D., Deusch, K., Seifirth, C., Funk, A., Dahie, I., Reut, K., Classen, M., Gionchetti, P., Vaira, D., Campieri, M., Bertinelli, E., Menegatti, M., Belluzzi, A., Briognola, C., Miglioli, M., Barbara, L., Tommaso, A. Di, Magistris, M. T. De, Bugnoli, M., Petracca, R., Covacci, A., Censini, S., Rappuoli, R., Abrignani, S., Territo, M. C., Smela, K. L., Reeve, J. R., Lee, T. D., Walsh, J. H., Armellini, D., Crabtree, J. E., Xiang, Z. Y., Mitchell, H. M., Hu, P. J., Li, Y. Y., Wang, Z. J., Zhao, S. M., Liu, Q., Chen, M., Du, G. G., Filipe, M. I., Reed, P. I., Craanen, M. E., Blok, P., Dekker, W., Colombo, E., Redaelli, D., Santangelo, M., Spinelli, M., Farinati, F., Valiante, F., Delia Libera, G., Germanà, B., Baffa, R., Rugge, M., Vianelo, F., Di Mario, F., Sipponen, Pentti, Rokkas, T., Popotheodorou, G., Kaldgeropoulos, N., Deprez, C., Galand, P., Fox, J. G., Wishnok, P., Murphy, J. C., Tannenbaum, S., Correa, P., Parsonnet, Julie, Macor, C., Da Broi, G. L., Avellinio, C., Reifen, R., Rasooly, I., Millson, M. E., Murphy, K., Thomas, J. E., Eastham, E. J., Malorgio, E., Dell’Olio, D., Kemmer, T. P., Dominguez-Munoz, J. E., Klingel, H., Gatto, M. R. A., Olivieri, R., Bayeli, R. F., Abate, L., De Gregorio, L., Aziz, J., Esposito, E., Basagni, C., Guilluy, R., Rousseau-Tsangaris, M., Brazier, J. L., Wadstiöm, Torkel, Tyszkiewicz, Tadeusz, Bergenzaun, Per, Olsson, Karin, Birac, C., Tall, F., Albenque, M., Labigne, A., Megraud, F., Feldman, R. A., Deeks, J., Glupczynski, Y., Burette, A., Goossens, H., Van den Boore, C., Butzler, J. P., Veldhuyzen van Zanten, S., Best, L., Benzanson, G., Haldane, D., Hazell, S., Mapstone, N. P., Lynch, D. A. F., Quirke, P., Taylor, D. E., Chang, N., Eaton, M., Stockdale, E., Salama, S. M., Thompson, L., Cockayne, A., Spiller, R. C., Leen, E., Sweeney, E., Klann, H., Hatz, R., Bornschein, W., Simon, T., Eimiller, A., Bolle, F., Schweikert, C., Köpeke, W., Moss, S. F., Bishop, A. E., Calam, J., Cahill, R. J., Xia, H., Solnick, J., and Tompkins, L.

Published
1992
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3. Forebyggelse af recidiv af ulcus doudeni med penicillin

Author

Rune, S.J., Justesen, J., Hansen, J.M., Jensen, T.G., Eriksen, J., Thomsen, O.Ø., Scheibel, J., Bonnevie, O., Bremmelgaard, A., Vilien, M., Knuhtsen, S., Elsborg, L., Hansen, J., Lauritsen, K., Wulff, H. R., Rune, S.J., Justesen, J., Hansen, J.M., Jensen, T.G., Eriksen, J., Thomsen, O.Ø., Scheibel, J., Bonnevie, O., Bremmelgaard, A., Vilien, M., Knuhtsen, S., Elsborg, L., Hansen, J., Lauritsen, K., and Wulff, H. R.

Abstract

Intern medicin

Published
1994

5. Prevention of Duodenal Ulcer Recurrence with Penicillin: A Double-Blind, Placebo-Controlled Trial

Author

Rune, S. J., primary, Justesen, T., additional, Hansen, J. Møller, additional, Jensen, T. Gorm, additional, Eriksen, J., additional, Thomsen, O. Østergaard, additional, Scheibel, J., additional, Bonnevie, O., additional, Bremmelgaard, A., additional, Vilien, M., additional, Knuhtsen, S., additional, Elsborg, L., additional, Hansen, J., additional, Lauritsen, K., additional, and Wulff, H. R., additional

Published
1993
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10. Role of GastrinReleasing Peptide in Neural Control of Pancreatic Exocrine Secretion

Author

Holst, J. J., Knuhtsen, S., and Nielsen, O. V.

Abstract

We studied the effect of electrical stimulation of the vagus nerves on the exocrine secretion of isolated perfused porcine pancreas before and after procedures that almost completely blocked the effects elicited by infusions of gastrin-releasing peptide (GRP): desensitization of the pancreas for GRP (by perfusion with high concentrations of GRP); administration of an antagonist of GRP action [D-Arg1, D-PrO2, D-Trp7,9, Leu11)-substance PI; and perfusion with Fab fragments of antibodies against GRP. Both desensitization and antagonist administration significantly (p < 0.01) inhibited the effect of vagus stimulation on pancreatic protein secretion (by 42.1 and 33). The inhibitory effect of anti-GRP perfusion was less pronounced (22 inhibition, 0.05 >p < 0.1). The results support the notion that pancreatic, GRP-producing nerve fibers are involved in the neural control of pancreatic enzyme secretion.

Published
1989

11. Molecular characterization of the solubilized receptor of somatostatin from rat pancreatic acinar membranes

Author

Knuhtsen, S, Esteve, J P, Bernadet, B, Vaysse, N, and Susini, C

Abstract

The somatostatin receptors on rat pancreatic acinar membranes were demonstrated by use of a radioiodinated (125I-) analogue of somatostatin (SMS 204-090 or [Tyr3]SMS). The tracer was found to bind to the receptor with a Kd of 58 pM. The number of sites detected by this tracer (4.7 pmol/mg of protein) was 5-10 times higher than the number of sites previously found with other tracers. Since the level of non-specific binding was also very low as compared with findings with other tracers, 125I-204-090 might be of interest in future attempts to characterize the somatostatin receptors in the pancreas. The prelabelled membranes were solubilized with 1% CHAPS, and the solubilized complexes were found to adsorb to wheat-germ-agglutinin-coupled agarose, from which they could be eluted with 4 mM-triacetylchitotriose. The complexes within this eluate were shown by gel filtration on Trisacryl GF-2000 to have an Mr of about 400,000. The dissociation of the complexes was augmented both within the membranes as well as in the solubilized state by incubation with the GTP analogue guanosine 5′-[gamma-thio]triphosphate, indicating that the complexes are probably functionally linked to a guanine-nucleotide-binding regulatory protein. After SDS/slab-gel electrophoresis and autoradiography of cross-linked complexes after treatment with the heterobifunctional reagent N-5-azido-2-nitrobenzoyloxysuccinimide, a broad band occurred at approximately Mr 90,000 both in the membranes and in the eluates of complexes after lectin-adsorption chromatography. We conclude that the augmentation of the number of detectable sites for binding of somatostatin, as well as the very low level of non-specific binding obtained by the use of 125I-[Tyr3]SMS as tracer, has made it possible for us to demonstrate the solubilization of the somatostatin receptor in conjunction with its ligand and a GTP-binding regulatory protein, and we have succeeded in cross-linking 125I-[Tyr3]SMS to a binding subunit of Mr 90,000 in the membranes and in demonstrating the presence of the same labelled binding subunit within complexes solubilized and chromatographed on a lectin column before cross-linking.

Published
1988
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12. Interrelation of nerves and hormones in stomach and pancreas

Author

Jens Juul Holst, Knuhtsen S, Sl, Jensen, Fahrenkrug J, Li, Larsson, and Ov, Nielsen

Subjects
Neurons, Swine, Stomach, Vagus Nerve, Gastric Inhibitory Polypeptide, Hydrogen-Ion Concentration, Electric Stimulation, Gastrin-Releasing Peptide, Gastrins, Pyloric Antrum, Animals, Bombesin, Gastric Fundus, Cholecystokinin, Peptides, Somatostatin, Pancreas, Vasoactive Intestinal Peptide
Abstract

Recent investigations have shown that the functions of the gastrointestinal organs may be regulated by a complex system of paracrine cells and peptidergic nerves, in addition to the established humoral and autonomic nervous systems. In this article we discuss the possible paracrine regulation of the secretory functions of the stomach and the pancreas by somatostatin-producing D-cells. Secondly, we discuss the distribution, localization, effects and secretion of the neuropeptides VIP and 'gastrin-releasing polypeptide' (GRP or 'mammalian bombesin') applied to the stomach (GRP) and pancreas (GRP and VIP) of the pig. It is concluded, that all three peptides are capable of influencing powerfully the secretory state of these organs, and that these newer regulatory peptides probably play an important role in the integrate neurohormonal control of gastrointestinal secretion.

Published
1983

13. On the regulatory functions of neuropeptide Y (NPY) with respect to vascular resistance and exocrine and endocrine secretion in the pig pancreas

Author

Holst, J J, Orskov, C, Knuhtsen, S, Sheikh, S, Nielsen, O V, Holst, J J, Orskov, C, Knuhtsen, S, Sheikh, S, and Nielsen, O V

Abstract

We compared the effects of electrical stimulation of the splanchnic nerves and infusions of neuropeptide Y, noradrenaline or a combination of the two on pancreatic vascular resistance and exocrine and endocrine secretion. For these studies we used isolated perfused pig pancreas with preserved splanchnic nerve supply. The exocrine secretion was stimulated with physiological concentrations of secretin and cholecystokinin octapeptide. Noradrenaline and NPY at 10(-8) M both increased pancreatic perfusion pressure. Their effects were additive and similar in magnitude to that of electrical stimulation of the splanchnic nerves at 4-8 Hz. Nerve stimulation as well as NPY and noradrenaline infusions inhibited exocrine secretion, but an additive effect could not be demonstrated. Neither NPY nor noradrenaline could reproduce the stimulatory effect of nerve stimulation on glucagon secretion, nor the weak inhibitory effect on somatostatin secretion. NPY alone had no effect on insulin secretion and did not influence the inhibitory effect of noradrenaline. It is concluded that NPY is likely to cooperate with noradrenaline in the control of pancreatic blood flow, whereas its role in the control of pancreatic secretion is likely to be of minor importance, if any.

Published
1989

15. Radioimmunoassay, pharmacokinetics, and neuronal release of gastrin-releasing peptide in anesthetized pigs

Author

Knuhtsen S, Jens Juul Holst, Knigge U, Olesen M, and Ov, Nielsen

Subjects
Neurons, Swine, Radioimmunoassay, Adrenalectomy, Vagus Nerve, Hydrogen-Ion Concentration, Electric Stimulation, Gastrointestinal Hormones, Kinetics, Gastrin-Releasing Peptide, Pyloric Antrum, Animals, Gastric Fundus, Peptides
Abstract

Using a newly developed radioimmunoassay for porcine gastrin-releasing peptide in plasma, we studied the pharmacokinetics of this peptide after infusing it into pigs at two dose levels. The disappearance of the peptide from plasma was characterized by two components, a fast one (t 1/2 1.4 min) and a slow one (t 1/2 6.6 min). With the same assay the release of gastrin releasing-peptide from the stomachs of 8 pigs that had been catheterized for selective sampling of fundic and antral blood was studied during vagal and splanchnic stimulation with or without acute adrenalectomy at neutral, acidic, and alkaline intragastric pH. Electrical stimulation of the vagal nerves resulted in a marked increase in both antral and fundic gastrin-releasing peptide release, whereas splanchnic stimulation was without effect. The effects of nerve stimulation were neither influenced by intragastric pH nor by adrenalectomy. Because of its presence in nerves in all layers of the gastric wall, its potent effect on gastrin release, and its release after vagal stimulation, gastrin-releasing peptide is likely to play a role in the vagal control of gastrin release, gastric motility, and acid secretion.

16. Role of gastrin-releasing peptide in neural control of pancreatic exocrine secretion

Author

J. J. Holst, O. V. Nielsen, and Knuhtsen S

Subjects
medicine.medical_specialty, Swine, Endocrinology, Diabetes and Metabolism, Stimulation, Peptide hormone, Biology, Endocrinology, Desensitization (telecommunications), Internal medicine, Gastrin-releasing peptide, Internal Medicine, medicine, Animals, Pancreas, Hepatology, Pancreatic Exocrine Secretion, Antagonist, Vagus Nerve, Electric Stimulation, medicine.anatomical_structure, Gastrin-Releasing Peptide, Gastrointestinal hormone, Peptides, hormones, hormone substitutes, and hormone antagonists
Abstract

We studied the effect of electrical stimulation of the vagus nerves on the exocrine secretion of isolated perfused porcine pancreas before and after procedures that almost completely blocked the effects elicited by infusions of gastrin-releasing peptide (GRP): desensitization of the pancreas for GRP (by perfusion with high concentrations of GRP); administration of an antagonist of GRP action [D-Arg1, D-Pro2, D-Trp7,9, Leu11)-substance P]; and perfusion with Fab fragments of antibodies against GRP. Both desensitization and antagonist administration significantly (p less than 0.01) inhibited the effect of vagus stimulation on pancreatic protein secretion (by 42.1 and 33%). The inhibitory effect of anti-GRP perfusion was less pronounced (22% inhibition, 0.05 greater than p less than 0.1). The results support the notion that pancreatic, GRP-producing nerve fibers are involved in the neural control of pancreatic enzyme secretion.

17. [Neuropeptides in health and disease]

Author

Jens Juul Holst, Knuhtsen S, Fahrenkrug J, Sl, Jensen, Ss, Poulsen, and Ov, Nielsen

Subjects
Neurotransmitter Agents, Protein Conformation, Pancreatic Neoplasms, Gastrin-Releasing Peptide, Gastric Mucosa, Gastrins, Pyloric Antrum, Animals, Humans, Cholecystokinin, Peptides, Somatostatin, Pancreas, Gastrointestinal Neoplasms, Vasoactive Intestinal Peptide

25. Direct Inhibitory Effects of a Somatostatin Analog, SMS 201-995, on AR4-2J Cell Proliferation via Pertussis Toxin-Sensitive Guanosine Triphosphate-Binding Protein-Independent Mechanism*

Author

VIGUERIE, N., primary, TAHIRI-JOUTI, N., additional, AYRAL, A. M., additional, CAMBILLAU, C., additional, SCEMAMA, J. L., additional, BASTIÉ, M. J., additional, KNUHTSEN, S., additional, ESTÈVE, J. P., additional, PRADAYROL, L., additional, SUSINI, C., additional, and VAYSSE, N., additional

Published
1989
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28. Transporter function and cyclic AMP turnover in normal colonic mucosa from patients with and without colorectal neoplasia

Author

Kleberg Karen, Jensen Gerda, Christensen Dan, Lundh Morten, Grunnet Lars, Knuhtsen Svend, Poulsen Steen, Hansen Mark, and Bindslev Niels

Subjects
Cyclic-AMP compartmentalization, Human colonic biopsy, OATP-, ABC-, PGE2-transporters, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background The pathogenesis of colorectal neoplasia is still unresolved but has been associated with alterations in epithelial clearance of xenobiotics and metabolic waste products. The aim of this study was to functionally characterize the transport of cyclic nucleotides in colonic biopsies from patients with and without colorectal neoplasia. Methods Cyclic nucleotides were used as model substrates shared by some OATP- and ABC-transporters, which in part are responsible for clearance of metabolites and xenobiotics from the colonic epithelium. On colonic biopsies from patients with and without colorectal neoplasia, molecular transport was electrophysiologically registered in Ussing-chamber set-ups, mRNA level of selected transporters was quantified by rt-PCR, and subcellular location of transporters was determined by immunohistochemistry. Results Of four cyclic nucleotides, dibuturyl-cAMP induced the largest short circuit current in both patient groups. The induced short circuit current was significantly lower in neoplasia-patients (p = 0.024). The observed altered transport of dibuturyl-cAMP in neoplasia-patients could not be directly translated to an observed increased mRNA expression of OATP4A1 and OATP2B1 in neoplasia patients. All other examined transporters were expressed to similar extents in both patient groups. Conclusions OATP1C1, OATP4A1, OATP4C1 seem to be involved in the excretory system of human colon. ABCC4 is likely to be involved from an endoplasmic-Golgi complex and basolateral location in goblet cells. ABCC5 might be directly involved in the turnover of intracellular cAMP at the basolateral membrane of columnar epithelial cells, while OATP2B1 is indirectly related to the excretory system. Colorectal neoplasia is associated with lower transport or sensitivity to cyclic nucleotides and increased expression of OATP2B1 and OATP4A1 transporters, known to transport PGE2.

Published
2012
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32. ERCP with single-use disposable duodenoscopes in four different set-ups.

Author

Lagström R, Knuhtsen S, Stigaard T, and Bulut M

Subjects
Humans, Cholangiopancreatography, Endoscopic Retrograde, Duodenoscopes
Abstract

Endoscopic retrograde cholangiopancreatography (ERCP) has until now always been performed using a reusable non-sterile duodenoscope. The introduction of the new single-use disposable duodenoscope makes it possible to perform perioperative transgastric and rendezvous ERCP in an almost sterile manner. It also eliminates the risk of patient-to-patient transmission of infection in non-sterile settings. We present four patients who underwent different types of ERCP using a sterile single-use duodenoscope. This case report aims to demonstrate the use and the many potential advantages of the new disposable single-use duodenoscope in both sterile and non-sterile settings., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2023
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35. Endoscopic full-thickness resection of benign and malignant colon lesions with one-year follow up in a Danish cohort.

Author

Bulut M, Buch N, Knuhtsen S, Gögenur I, and Bremholm L

Subjects
Colon, Denmark, Follow-Up Studies, Humans, Prospective Studies, Retrospective Studies, Treatment Outcome, Endoscopic Mucosal Resection methods, Neoplasm Recurrence, Local etiology
Abstract

Background: Endoscopic full-thickness resection (EFTR) has been shown to be a feasible and safe technique in several studies since the introduction of the full-thickness resection device (FTRD ® ). This study aimed to describe our clinical experience and long-term follow up in in patients who underwent EFTR of benign and malignant colon lesions using FTRD., Methods: All patients with difficult adenomas or early adenocarcinomas referred for an EFTR to two centres in Denmark were included in this prospective consecutive study. The primary outcome was technical success with R0 resection and relapse-free follow up. The secondary outcome was procedure-related adverse events., Results: Twenty-six patients were enrolled in the study. Technical success was achieved in 81% patients and R0 resection rate was 86%. Full-thickness resection was achieved in 86% patients. In 13 patients with malignant lesions, we obtained follow-up in 10 cases (two patients underwent surgery and one was non-compliant). Findings of the three-month follow up showed no residual tumour in all 10 cases. At the 12-month follow up, one patient had a late relapse. There were no residual or recurrent adenomas in the benign subgroup. Overall, adverse events were observed in 11.5% (3/26) patients with a perforation rate of 7.7%., Conclusion: EFTR with FTRD proves to be an additional technique for the treatment of difficult non-lifting colorectal lesions. For malignant lesions, EFTR is technically safe and feasible and can potentially treat small early low-risk tumours; however, some cases may require subsequent surgery according to the histological staging observed in the resected specimen.

Published
2022
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36. Combined endoscopic laparoscopic surgical treatment of advanced adenomas and early colon cancer.

Author

Bulut M, Knuhtsen S, Holm FS, Eriksen JR, Gögenur I, and Bremholm L

Subjects
Adult, Aged, Aged, 80 and over, Colon pathology, Denmark, Female, Humans, Length of Stay, Male, Middle Aged, Retrospective Studies, Adenoma surgery, Colonic Neoplasms surgery, Colonic Polyps surgery, Colonoscopy methods, Laparoscopy methods
Abstract

Introduction: A subgroup of patients with benign colonic neoplasia is unsuitable for standard endoscopic treatment modalities. These patients may benefit from a combined endoscopic and laparoscopic surgical (CELS) approach. A CELS procedure may even be an option for some patients with a small malignant lesion where resection of the colon may be associated with an excessively high risk of proced-ure-related morbidity and mortality., Methods: All patients considered for a CELS procedure were evaluated at a multidisciplinary team conference. The CELS procedures were performed as laparoscopy-assisted endoscopic mucosal resections or endoscopy-assisted laparoscopic resections., Results: A total of 25 patients were included. Five patients had a malignant and 20 patients had a benign lesion. Two patients with histologically verified malignant lesions pre-operatively had CELS performed due to severe co-morbidity. In one patient with initially benign biopsies, the resected CELS specimen revealed adenocarcinoma. This patient subsequently underwent oncological resection (no residual disease). In the last two cases, the lesions were assessed during CELS and they exhibited endoscopically malignant features. Consequently, both patients underwent immediate oncological segmental colon resection., Conclusions: CELS is a feasible treatment for colonic neoplasia where endoscopic resection alone is not technically possible. In case of severe co-morbidity ruling out segmental resection in patients diagnosed with T1 or T2 colorectal cancer, CELS treatment may be considered., Funding: none., Trial Registration: This study was assessed by The National Committee on Health Research Ethics (SJ-593), which concluded that the study required no approval from the Committee. The study was approved by the Danish Data Protection Agency (REG-126-2017). ., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Published
2019

37. [Colonoscopy following acute diverticulitis mandatory].

Author

Erritzøe LW, Knuhtsen S, and Hansen LB

Subjects
Acute Disease, Humans, Retrospective Studies, Tomography, X-Ray Computed, Colonoscopy, Diverticulitis, Diverticulitis, Colonic
Abstract

According to international guidelines, patients presenting with acute diverticulitis are offered lower endoscopy to rule out colorectal cancer. This practice is based on weak evidence. Recent studies have established that the incidence of colorectal cancer after acute diverticulitis is low. In case of complicated diverticulitis, with abscess or perforation, the incidence of colorectal cancer is higher. There is, thus, a lack of evidence supporting colonoscopy by uncomplicated diverticulitis, but if a patient presents with complicated diverticulitis, colonoscopy should be performed.

Published
2018

38. Duodenal epithelial transport in functional dyspepsia: Role of serotonin.

Author

Witte AB, D'Amato M, Poulsen SS, Laurent A, Knuhtsen S, Bindslev N, Hansen MB, and Schmidt PT

Abstract

Aim: To investigate functional duodenal abnormalities in functional dyspepsia (FD) and the role of serotonin (5-hydroxytryptamine, 5-HT) in mucosal ion transport and signalling., Methods: Duodenal mucosal biopsies were obtained from 15 patients with FD and 18 healthy controls. Immunohistochemistry was used to study the number of 5-HT-containing cells and real-time polymerase chain reaction for expression of 5-HT receptors 1A, 1B, 2A, 2B, 3A, 3B, 3C, 3D, 3E, 4 and 7, as well as expression of the serotonin re-uptake transporter (SERT) gene SLC6A4 and tryptophan hydroxylase 1 (TPH1). Biopsies were mounted in Ussing chambers for evaluation of basal and 5-HT-stimulated short-circuit current (SCC)., Results: Conductance was lower in FD [42.4 ± 4.7 mS/cm(2) (n = 15) vs 62.5 ± 4.5 mS/cm(2) (n = 18), P = 0.005]. 5-HT induced a dose dependent rise in SCC in both FD (n = 8) and controls (n = 9), the rise was lower in FD (P < 0.001). Mean number of 5-HT stained cells per high power field was the same [34.4 ± 8.4 in FD (n = 15) and 30.4 ± 3.7 in controls (n = 18), P = 0.647]. The following genes were highly expressed: 5-HT receptor HTR3E, HTR4, HTR7, SERT gene (SLC6A4) and TPH1. Differences in expression levels were observed for HTR3E (higher expression in FD, P = 0.008), HTR7 (lower expression in FD, P = 0.027), SLC6A4 (higher expression in FD, P = 0.033) and TPH1 (lower expression in FD, P = 0.031)., Conclusion: Duodenal ion transport in response to exogenous 5-HT is abnormal in FD patients and associated with high expression of the HTR3E receptor and the serotonin transporter.

Published
2013
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39. [Colonic malacoplakia treated with sulfamethizole and trimethoprim].

Author

Christensen M, Knuhtsen S, and Knudsen E

Subjects
Aged, Colon, Transverse microbiology, Colon, Transverse pathology, Colonic Diseases microbiology, Colonic Diseases pathology, Colonoscopy, Drug Therapy, Combination, Female, Humans, Malacoplakia microbiology, Malacoplakia pathology, Treatment Outcome, Anti-Infective Agents therapeutic use, Colonic Diseases drug therapy, Malacoplakia drug therapy, Sulfamethizole therapeutic use, Trimethoprim therapeutic use
Abstract

We report a case of colonic malacoplakia in a 78-year-old woman, developed following short-term treatment with prednisolone. Clinically, the patient presented with diarrhoea (up to ten times a day) and malaise. Laboratory tests revealed severe anaemia and elevated inflammatory parameters. Colonoscopy showed macroscopic yellowish nodular changes throughout the colon. Biopsies were diagnostic for malacoplakia and exhibited moderate growth of Escherichia faecium and ciprofloxacin-resistant Escherichia coli. The condition resolved during three months of antibiotic treatment with sulfamethizole and trimethoprim.

Published
2011

40. Gastrin-releasing peptide: pharmacokinetics and effects on gastro-entero-pancreatic hormones and gastric secretion in normal men.

Author

Knigge U, Holst JJ, Knuhtsen S, Petersen B, Krarup T, Holst-Pedersen J, and Christiansen PM

Subjects
Adult, Blood Glucose metabolism, Dose-Response Relationship, Drug, Gastric Acid metabolism, Gastrin-Releasing Peptide, Gastrins metabolism, Humans, Kinetics, Male, Peptides metabolism, Gastrointestinal Hormones metabolism, Pancreatic Hormones metabolism, Peptides pharmacology
Abstract

Gastrin-releasing peptide (GRP) was infused at two dose levels [GRP I (0-30 min): bolus dose of 1.41 pmol kg-1, followed by 0.12 pmol kg-1 min-1; GRP II (30-60 min): bolus dose of 5.67 pmol kg-1, followed by 1.50 pmol kg-1 min-1] to six normal men to study the pharmacokinetics of GRP using a newly developed RIA and the effect of GRP on gastro-entero-pancreatic hormones and gastric acid secretion. The half-life of disappearance of GRP was 2.8 +/- 0.4 min (+/- SEM). The MCR and the apparent space of distribution were 33.0 +/- 4.0 ml kg-1 min-1 and 133 +/- 31 ml kg-1, respectively. GRP stimulated the secretion of gastrin, pancreatic polypeptide, insulin, glucagon, and glucose-dependent insulinotropic polypeptide in a dose-dependent manner. Gastric acid secretion was stimulated 15 min after the increase in gastrin secretion, suggesting that GRP stimulated gastric acid secretion via release of gastrin. GRP had no significant effect on the secretion of enteroglucagon or neurotensin. In the mammalian gastrointestinal tract, GRP is localized exclusively to nerve tissue. This fact and its potent effects demonstrated here make it a likely candidate for peptidergic nervous control of gastrointestinal function.

Published
1984
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41. Gastrin-releasing peptide in the porcine pancreas.

Author

Knuhtsen S, Holst JJ, Baldissera FG, Skak-Nielsen T, Poulsen SS, Jensen SL, and Nielsen OV

Subjects
Animals, Chromatography, Gel, Gastrin-Releasing Peptide, Immunoenzyme Techniques, Pancreas anatomy & histology, Radioimmunoassay, Swine, Tissue Extracts, Pancreas analysis, Peptides analysis
Abstract

The presence of gastrin-releasing peptide (GRP) was studied in extracts of porcine pancreata. Gel filtration and high-pressure liquid chromatographic profiles of these extracts as monitored with both C-terminally and N-terminally directed radioimmunoassays against GRP showed pancreatic GRP to consist of one main form, namely the 27-amino acid peptide originally extracted from porcine stomach, and small amounts of a C-terminal fragment identical with the C-terminal 10-amino acid peptide. Gastrin-releasing peptide-like immunoreactivity released from the isolated perfused porcine pancreas during electrical vagal stimulation was shown by gel filtration to consist of the same two forms. By use of immunocytochemical techniques employing an antiserum directed against its N terminus, GRP was localized to varicose nerve fibers in close association with the exocrine tissue of the porcine pancreas in particular. Some fibers were found penetrating into pancreatic islets also. Immunoreactive nerve cell bodies as well as fibers were found within intrapancreatic ganglia. The potency of GRP in stimulating exocrine as well as endocrine secretion from the porcine pancreas, its presence in close contact with both acini and islets, and its release during vagal stimulation indicate that GRP may have a role in the parasympathetic regulation of endocrine and exocrine secretion from the pig pancreas.

Published
1987
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42. Oxyntomodulin (glicentin-(33-69)): pharmacokinetics, binding to liver cell membranes, effects on isolated perfused pig pancreas, and secretion from isolated perfused lower small intestine of pigs.

Author

Baldissera FG, Holst JJ, Knuhtsen S, Hilsted L, and Nielsen OV

Subjects
Animals, Cell Membrane metabolism, Chromatography, Gel, Chromatography, High Pressure Liquid, Glucagon metabolism, Glucagon-Like Peptides metabolism, Glucagon-Like Peptides pharmacology, Guinea Pigs, In Vitro Techniques, Islets of Langerhans drug effects, Oxyntomodulin, Perfusion, Radioimmunoassay, Receptors, Glucagon, Gastrointestinal Hormones pharmacokinetics, Glucagon-Like Peptides pharmacokinetics, Ileum metabolism, Islets of Langerhans metabolism, Liver metabolism, Receptors, Gastrointestinal Hormone metabolism
Abstract

The pharmacokinetics of purified synthetic oxyntomodulin were studied after infusing it into euglycaemic pigs at two rates. The elimination of the peptide from plasma was characterized by two components, a fast one (t1/2 7.2 +/- 0.6 min) and a slow one (t1/2 20.4 +/- 3.8 min) (mean +/- S.E.M., n = 7). The metabolic clearance rate was independent of infusion rate (6.96 +/- 0.99 vs 7.44 +/- 0.98 ml/kg . min (mean +/- S.E.M., n = 7). The synthetic peptide bound to pig hepatic glucagon receptors, but with approximately 2% of the affinity of glucagon, and showed insulinotropic and somatostatinotropic effects when infused into isolated perfused pig pancreases at concentrations higher than 10(-10) M. A dose-dependent increase was also shown for pancreatic glucagon output. A naturally occurring peptide, identified as oxyntomodulin by gel filtration and HPLC, was released into the circulation from the pig lower small intestinal mucosa upon intraluminal administration of glucose, and represented 25 +/- 3.8% of the secreted glucagon-like immunoreactivity. 11 +/- 2.3% of the secreted glucagon-like immunoreactivity was indistinguishable from glucagon itself upon gel filtration; thus at least 36% of the glucagon-like immunoreactivity secreted from the intestinal mucosa is already in an active form.

Published
1988
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43. Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas.

Author

Orskov C, Holst JJ, Knuhtsen S, Baldissera FG, Poulsen SS, and Nielsen OV

Subjects
Animals, Arginine pharmacology, Gastrin-Releasing Peptide, Glucagon metabolism, Glucagon-Like Peptide 1, Glucagon-Like Peptide 2, Glucose pharmacology, Histocytochemistry, Immunoenzyme Techniques, Intestine, Small analysis, Intestine, Small drug effects, Pancreas analysis, Pancreas drug effects, Peptides analysis, Peptides pharmacology, Proglucagon, Protein Precursors metabolism, Swine, Intestine, Small metabolism, Pancreas metabolism, Peptides metabolism
Abstract

We developed specific antibodies and RIAs for glucagon-like peptides 1 and 2 (GLP-1 and GLP-2), two predicted products of the glucagon gene, and studied the occurrence, nature, and secretion of immunoreactive GLP-1 and GLP-2 in pig pancreas and small intestine. Immunoreactive GLP-1 and GLP-2 were identified in glucagon-producing cells of the pancreatic islets, and in glicentin-producing cells of the small intestine. Immunoreactive GLP-1 and 2 in intestinal extracts corresponded in molecular size to peptides synthesized according to the predicted structure. By reverse phase HPLC, intestinal and synthetic GLP-1 behaved similarly, whereas synthetic and intestinal GLP-2 differed. Pancreatic extracts contained a large peptide with both GLP-1 and GLP-2 immunoreactivity. Secretion was studied using isolated perfused pig pancreas during arginine stimulation, and isolated perfused pig ileum during either luminal glucose stimulation or vascular administration of the neuropeptide, gastrin-releasing peptide (GRP). Immunoreactive GLP-1 and GLP-2 were secreted in parallel with pancreatic glucagon and intestinal glicentin. The molecular forms of secreted immunoreactive GLP-1 and 2 corresponded to those identified in the tissue extracts.

Published
1986
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44. Vasoactive intestinal polypeptide (VIP) in the pig pancreas: role of VIPergic nerves in control of fluid and bicarbonate secretion.

Author

Holst JJ, Fahrenkrug J, Knuhtsen S, Jensen SL, Poulsen SS, and Nielsen OV

Subjects
Animals, Electric Stimulation, Immunoenzyme Techniques, Pancreas innervation, Perfusion, Swine, Vagus Nerve physiology, Bicarbonates metabolism, Pancreas physiology, Pancreatic Juice metabolism, Vasoactive Intestinal Peptide physiology
Abstract

Vasoactive intestinal polypeptide (VIP) in the pig pancreas is localized to nerves, many of which travel along the pancreatic ducts. VIP stimulates pancreatic fluid and bicarbonate secretion like secretin. Electrical vagal stimulation in the pig causes an atropine-resistant profuse secretion of bicarbonate-rich pancreatic juice. In an isolated perfused preparation of the pig pancreas with intact vagal nerve supply, electrical vagal stimulation caused an atropine-resistant release of VIP, which accurately parallelled the exocrine secretion of juice and bicarbonate. Perfusion of the pancreas with a potent VIP-antiserum inhibited the effect of vagal stimulation on the exocrine secretion. It is concluded, that VIP is responsible for (at least part of) the neurally controlled fluid and bicarbonate secretion from the pig pancreas.

Published
1984
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45. [Neuropeptides in health and disease].

Author

Holst JJ, Knuhtsen S, Fahrenkrug J, Jensen SL, Poulsen SS, and Nielsen OV

Subjects
Animals, Cholecystokinin physiology, Gastric Mucosa innervation, Gastrin-Releasing Peptide, Gastrins physiology, Gastrointestinal Neoplasms etiology, Humans, Pancreas innervation, Pancreatic Neoplasms etiology, Peptides physiology, Protein Conformation, Pyloric Antrum innervation, Somatostatin physiology, Vasoactive Intestinal Peptide physiology, Neurotransmitter Agents physiology
Published
1985

47. Radioimmunoassay, pharmacokinetics, and neuronal release of gastrin-releasing peptide in anesthetized pigs.

Author

Knuhtsen S, Holst JJ, Knigge U, Olesen M, and Nielsen OV

Subjects
Adrenalectomy, Animals, Electric Stimulation, Gastric Fundus metabolism, Gastrin-Releasing Peptide, Gastrointestinal Hormones blood, Hydrogen-Ion Concentration, Kinetics, Neurons metabolism, Peptides blood, Pyloric Antrum metabolism, Swine, Vagus Nerve physiology, Gastric Fundus innervation, Gastrointestinal Hormones metabolism, Peptides metabolism, Pyloric Antrum innervation, Radioimmunoassay
Abstract

Using a newly developed radioimmunoassay for porcine gastrin-releasing peptide in plasma, we studied the pharmacokinetics of this peptide after infusing it into pigs at two dose levels. The disappearance of the peptide from plasma was characterized by two components, a fast one (t 1/2 1.4 min) and a slow one (t 1/2 6.6 min). With the same assay the release of gastrin releasing-peptide from the stomachs of 8 pigs that had been catheterized for selective sampling of fundic and antral blood was studied during vagal and splanchnic stimulation with or without acute adrenalectomy at neutral, acidic, and alkaline intragastric pH. Electrical stimulation of the vagal nerves resulted in a marked increase in both antral and fundic gastrin-releasing peptide release, whereas splanchnic stimulation was without effect. The effects of nerve stimulation were neither influenced by intragastric pH nor by adrenalectomy. Because of its presence in nerves in all layers of the gastric wall, its potent effect on gastrin release, and its release after vagal stimulation, gastrin-releasing peptide is likely to play a role in the vagal control of gastrin release, gastric motility, and acid secretion.

Published
1984

48. The effect of gastrin-releasing peptide on the endocrine pancreas.

Author

Knuhtsen S, Holst JJ, Schwartz TW, Jensen SL, and Nielsen OV

Subjects
Animals, Atropine pharmacology, Gastrin-Releasing Peptide, Glucose pharmacology, Insulin metabolism, Insulin Secretion, Islets of Langerhans metabolism, Pancreatic Polypeptide metabolism, Somatostatin metabolism, Swine, Islets of Langerhans drug effects, Peptides pharmacology
Abstract

The 27-amino acid peptide gastrin releasing peptide (GRP-(1-27] was infused at 4 dose levels (0.01, 0.1, 1.0, and 10 nM) into the arterial line of the isolated perfused porcine pancreas. Infusions were performed at 3 different perfusate glucose levels (3.5, 5.0, and 8.0 mM) and at two levels of amino acids (5 and 15 mM). GRP-(1-27) stimulated insulin and pancreatic polypeptide secretion and inhibited somatostatin secretion in a dose-dependent manner. Glucagon secretion was unaffected by infusion of GRP under all circumstances. The effect of GRP-(1-27) on insulin secretion was enhanced with increasing perfusate glucose levels, whereas the effects upon somatostatin and pancreatic polypeptide secretion were independent of perfusate glucose levels. The responses to GRP were unaffected by elevation of the concentration of amino acids in the perfusate. The effects of GRP were unaffected by atropine at 10(-6) M. The localization of GRP within the porcine pancreas, its release during electrical stimulation of the vagus nerve, and its potent effects upon pancreatic endocrine secretion make it conceivable that the peptide participates in parasympathetic regulation of pancreatic endocrine secretion.

Published
1987
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49. Interrelation of nerves and hormones in stomach and pancreas.

Author

Holst JJ, Knuhtsen S, Jensen SL, Fahrenkrug J, Larsson LI, and Nielsen OV

Subjects
Animals, Bombesin metabolism, Cholecystokinin physiology, Electric Stimulation, Gastric Fundus metabolism, Gastric Inhibitory Polypeptide pharmacology, Gastrin-Releasing Peptide, Gastrins physiology, Hydrogen-Ion Concentration, Neurons metabolism, Pancreas innervation, Peptides physiology, Pyloric Antrum metabolism, Somatostatin physiology, Stomach innervation, Swine, Vagus Nerve physiology, Vasoactive Intestinal Peptide physiology, Pancreas metabolism, Stomach physiology
Abstract

Recent investigations have shown that the functions of the gastrointestinal organs may be regulated by a complex system of paracrine cells and peptidergic nerves, in addition to the established humoral and autonomic nervous systems. In this article we discuss the possible paracrine regulation of the secretory functions of the stomach and the pancreas by somatostatin-producing D-cells. Secondly, we discuss the distribution, localization, effects and secretion of the neuropeptides VIP and 'gastrin-releasing polypeptide' (GRP or 'mammalian bombesin') applied to the stomach (GRP) and pancreas (GRP and VIP) of the pig. It is concluded, that all three peptides are capable of influencing powerfully the secretory state of these organs, and that these newer regulatory peptides probably play an important role in the integrate neurohormonal control of gastrointestinal secretion.

Published
1983

50. Corticotropin-releasing activity of gastrin-releasing peptide in normal men.

Author

Knigge U, Holst JJ, Knuhtsen S, Bach FW, and Bang P

Subjects
Adult, Animals, Dogs, Dose-Response Relationship, Drug, Gastrin-Releasing Peptide, Growth Hormone metabolism, Humans, Hydrocortisone metabolism, Male, Prolactin metabolism, Rats, beta-Endorphin metabolism, Adrenocorticotropic Hormone metabolism, Peptides pharmacology
Abstract

Gastrin-releasing peptide (GRP; mammalian bombesin) exerts several functions within the hypothalamus and is a putative regulator of pituitary hormone secretion. We investigated the effect of GRP on the secretion of pituitary hormones and cortisol in normal men. GRP was infused iv as primed infusions of 0.12 pmol/kg BW. min for 30 min (GRP I) and 1.50 pmol/kg. min for an additional 30 min (GRP II). GRP dose-dependently stimulated ACTH secretion compared with the effect of saline [net change in ACTH (delta ACTH) before and after treatment: GRP I, 3 +/- 1 (+/- SEM) vs. 0 +/- 1 pmol/L (P less than 0.05); GRP II, 5 +/- 1 vs. -3 +/- 1 pmol/L; P less than 0.01)]. A further increase in plasma ACTH concentration occurred after cessation of GRP infusion (7 +/- 2 vs. 0 +/- 1 pmol/L; P less than 0.025). GRP caused a similar dose-dependent stimulation of cortisol secretion compared with the effect of saline [delta cortisol before and after treatment: GRP I, -19 +/- 21 vs. -68 +/- 14 nmol/L (P less than 0.05); GRP II, 38 +/- 33 vs. -86 +/- 15 nmol/L (P less than 0.005)]. The serum cortisol concentration increased further after cessation of the GRP infusion (72 +/- 31 vs. -124 +/- 33 nmol/L; P less than 0.0025). GRP dose-dependently stimulated beta-endorphin immunoreactivity compared with the effect of saline [delta beta-endorphin immunoreactivity before and after treatment: GRP I, 6 +/- 1 vs. -3 +/- 1 pmol/L (P less than 0.01); GRP II, 11 +/- 4 vs. -6 +/- 2 pg/mL (P less than 0.025)]. GRP had no effect on PRL or GH secretion. We suggest that GRP participates in the neuroendocrine regulation of the secretion of proopiomelanocortin-derived peptides.

Published
1987
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