RESUMEN
Glucagon-like peptide-2 (GLP-2), an intestinal product of glucagon gene expression which induces intestinal growth in mice, has been proposed as a treatment for intestinal insufficiency. GLP-2 is metabolized extensively by dipeptidyl peptidase IV (DPP-IV) in rats, but less is known about its fate in humans. Therefore, GLP-2 metabolism was investigated in healthy volunteers after 1) a 500-Cal mixed meal (n = 6), 2) iv infusion of synthetic human GLP-2 (0.8 pmol/kg x min; n = 8), 3) a sc bolus injection (400 microg; n = 9), and 4) in vitro incubation in plasma and blood (1,000 pmol/L; n = 4). GLP-2 concentrations were determined by N-terminal RIA measuring only intact GLP-2, side-viewing RIA measuring intact and degraded forms [e.g. GLP-2-(3-33) arising from DPP-IV degradation], and high performance liquid chromatography (HPLC). Meal ingestion elevated plasma GLP-2 (intact, 16 +/- 3 to 73 +/- 10 pmol/L at 90 min), and HPLC revealed two immunoreactive components: intact GLP-2 (57 +/- 2%) and GLP-2-(3-33). GLP-2 infusion increased plasma levels [intact, 9 +/- 4 to 131 +/- 11 pmol/L; total, 23 +/- 7 to 350 +/- 18 pmol/L; the differences represent GLP-2-(3-33)]. The elimination t(1/2) values were 7.2 +/- 2 min (intact GLP-2) and 27.4 +/- 5.4 min [GLP-2-(3-33)], and MCRs were 6.8 +/- 0.6 and 1.9 +/- 0.3 mL/kg x min, respectively. Subcutaneous injection increased intact GLP-2 to maximally 1,493 +/- 250 pmol/L at 45 min, whereas total GLP-2 increased to 2,793 +/- 477 pmol/L at 90 min. At 60 min, plasma contained 69 +/- 1% intact GLP-2. In vitro the t(1/2) values were 8.0 +/- 1.5 h (plasma) and 3.3 +/- 0.3 h (blood). GLP-2-(3-33) was the only degradation product identified by HPLC, and a DPP-IV inhibitor abolished the degradation of GLP-2 in vitro. We conclude that GLP-2 is extensively degraded to GLP-2-(3-33) in humans, presumably by DPP-IV. Nevertheless, 69% remains intact 1 h after GLP-2 injection, supporting the possibility of sc use in patients with intestinal insufficiency.
Asunto(s)
Fragmentos de Péptidos/metabolismo , Péptidos/metabolismo , Adulto , Animales , Femenino , Péptido 2 Similar al Glucagón , Péptidos Similares al Glucagón , Humanos , Infusiones Intravenosas , Inyecciones Subcutáneas , Cinética , Masculino , Ratones , Persona de Mediana Edad , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/sangre , Péptidos/administración & dosificación , Péptidos/sangre , Periodo Posprandial , Ratas , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/sangre , Proteínas Recombinantes/metabolismoRESUMEN
BACKGROUND: Gastric lipase contributes significantly to overall lipolysis and is regulated by interacting neuro-hormonal mechanisms. Patients with alcoholic chronic pancreatitis (ACP) have low, or even absent, activity of pancreatic lipases. In that state the secretion of gastric lipase could be essential and compensate for the pancreatic defect. However, conflicting studies have not resolved the order of magnitude of gastric lipase secretion in these patients. This could be explained by differences in regulatory mechanisms, gastric mucosal changes, and abdominal vagal tone. METHODS: Nasogastric intubation with modified sham feeding and upper endoscopy including biopsies for histologic classification and Helicobacter pylori infection status were performed in eight ACP patients, and eight healthy volunteers were studied on separate occasions. Vagal nerve function was assessed by calculation of heart rate variability in ACP patients. Gastric lipase was measured in aspirates by means of enzyme-linked immunosorbent assay and an enzyme kinetic assay. Plasma concentrations of gastrin, secretin, cholecystokinin, and pancreatic polypeptide were measured throughout the study. RESULTS: Sham feeding rapidly and significantly increased gastric lipase secretion in healthy volunteers, whereas ACP patients did not respond to sham feeding. Two of eight patients were infected with H. pylori and had mucosal changes accordingly. The lack of lipase response could not be ascribed to dysfunction of the abdominal vagus. CONCLUSIONS: The cephalic phase of gastric lipase secretion is impaired in ACP patients. Although their fundic cells continue to secrete gastric lipase, they are not subject to normal neuro-hormonal regulation.
Asunto(s)
Insuficiencia Pancreática Exocrina/enzimología , Lipasa/metabolismo , Lipólisis/fisiología , Adulto , Biopsia , Enfermedad Crónica , Endoscopía del Sistema Digestivo , Nutrición Enteral , Femenino , Ácido Gástrico/metabolismo , Gastrinas/metabolismo , Gastritis/patología , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis Alcohólica/enzimologíaRESUMEN
BACKGROUND: The aim of the present investigation was to study gastric acid secretion and release of gastrin, cholecystokinin (CCK), and secretin during intraduodenal perfusion of either fish oil or trioleate. METHODS: Seven healthy volunteers were stimulated on two separate days in random order with intraduodenal perfusates of either fish oil or trioleate. RESULTS: Intravenous infusion with gastrin-17 was used as a background stimulation in doses mimicking a postprandial situation (39.9 +/- 4.8 pmol/l fish oil and 43.6 +/- 3.8 pmol/l trioleate). Gastric acid secretion increased significantly from a basal level of 0.7 +/- 0.1 meq/15 min to 4.0 +/- 0.6 meq/15 min (P < 0.05) before perfusion of fish oil, which reduced gastric acid secretion to 1.9 +/- 0.4 meq/15 min (P < 0.01). After termination of fish oil perfusion gastric acid secretion increased to preperfusion concentrations (P < 0.01). Perfusion of trioleate did not influence gastric acid secretion. Plasma concentrations of CCK rose significantly during perfusion of fish oil (from 2.8 +/- 0.6 pmol/l to 4.4 +/- 0.7pmol/l, P<0.01), whereas trioleate only tended to increase CCK concentrations. Plasma concentrations of secretin did not change during perfusion of fish oil; however, concentrations were significantly lower during and after perfusion of trioleate (P < 0.01). CONCLUSION: The present study shows that intraduodenal perfusion of fish oil is associated with a significant reduction of the gastric acid secretion stimulated by gastrin in healthy humans.
Asunto(s)
Aceites de Pescado/farmacología , Ácido Gástrico/metabolismo , Trioleína/farmacología , Adulto , Colecistoquinina/sangre , Colecistoquinina/metabolismo , Duodeno , Femenino , Aceites de Pescado/administración & dosificación , Gastrinas/administración & dosificación , Gastrinas/sangre , Gastrinas/metabolismo , Humanos , Masculino , Perfusión , Secretina/sangre , Secretina/metabolismo , Estadísticas no Paramétricas , Trioleína/administración & dosificaciónRESUMEN
In colorectal surgery, the double-stapled technique is used extensively, because it is a fairly safe and simple procedure and is useful in relatively inaccessible areas. For these reasons, we adapted the procedure to the upper gastrointestinal tract. The present study reports our first experiences of the surgical efficacy using an esophagogastric double-stapled end-to-end anastomosis for subtotal esophagectomy and cardia resection. We retrospectively studied 31 patients treated between January 1991 and January 1997 with respect to hospital mortality, anastomotic leakage, cancer recurrence, and benign stricture rate. No hospital mortality was seen. One nonfatal anastomotic leak occurred (3%). In three patients, esophageal resection was not radical (10%). Of the remaining 28 patients, one had an anastomotic cancer recurrence (4%). Eleven of the remaining 27 patients (41%) developed a benign anastomotic stricture. All achieved normal swallowing after a median of two endoscopic dilatation procedures using TTS balloons. In conclusion, the double-stapled end-to-end anastomosis technique after resection for esophagogastric or cardia cancer is a simple and expeditious procedure, carrying an acceptable perioperative morbidity and cancer recurrence rate. Larger staplers are recommended to lower the high stricture rate observed after the usage of a 21-mm stapler in this study.
Asunto(s)
Anastomosis Quirúrgica/métodos , Cardias/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Unión Esofagogástrica , Neoplasias Gástricas/cirugía , Suturas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Glucagon-like peptide (GLP)-2 is formed from proglucagon in the intestinal L cells and is secreted postprandially in parallel with the insulinotropic hormone GLP-1, the latter of which, in addition, acts to inhibit gastric secretion and motility by inhibiting central parasympathetic outflow. We now studied the effect of GLP-2 on gastric secretion stimulated by sham feeding to test the hypothesis that also GLP-2 acts as an enterogastrone. Eight healthy volunteers were studied twice on separate days. They were sham fed with and without GLP-2 infused iv at a rate of 0.8 pmol/kg x min. Gastric contents were aspirated continuously by a nasogastric tube for determination of acid secretion, volume, and osmolarity. Sham feeding increased gastric acid secretion nearly 5-fold. Infusion of GLP-2 reduced incremental acid secretion by 65+/-6%, compared with saline infusion (delta8.75+/-0.37 vs. delta3.04+/-0.47 mmol x 60 min; P<0.01). Plasma concentrations of GLP-2 rose from a basal mean of 3.3+/-0.9 to a mean of 115+/-8 pmol/L (range, 57-149 pmol/L) during infusion of GLP-2 and remained at basal level during saline infusion. Plasma concentrations of GLP-1, gastrin, cholecystokinin, and secretin remained low and unchanged on both study days. We conclude that GLP-2 is a powerful inhibitor of gastric acid secretion in man. Further investigations will show to what extent GLP-2 contributes to the inhibitory effects on gastric secretion exerted by hormones from the distal small intestine, under physiological circumstances.
Asunto(s)
Ácido Gástrico/metabolismo , Hormonas Gastrointestinales/farmacología , Péptidos/farmacología , Colecistoquinina/sangre , Gastrinas/sangre , Hormonas Gastrointestinales/administración & dosificación , Glucagón/sangre , Péptido 1 Similar al Glucagón , Péptido 2 Similar al Glucagón , Humanos , Infusiones Intravenosas , Fragmentos de Péptidos/sangre , Péptidos/administración & dosificación , Péptidos/fisiología , Precursores de Proteínas/sangre , Secretina/sangreRESUMEN
Seven healthy volunteers were intubated with two double lumen nasogastric tubes, one in the stomach, the other in the duodenum. This system allows simultaneous sampling of gastric juice and separate intraduodenal perfusion with a dietary fat (fish oil, 1269 kJ). Gastrin-17 was infused i.v. at a rate of 40 pmol/kg/h throughout the study. Gastric lipase was measured at 15-min intervals as activity (tributyrin) and as immunoreactivity (ELISA). Infusion of gastrin-17 resulted in a stable increase in the plasma concentration from a basal concentration of 8.3 +/- 0.8 pmol/l to 41.4 +/- 4.2 pmol/l. Perfusion with fat reduced gastric lipase activity from 24.2 +/- 5.3 to 7.2 +/- 2.5 kU/l (P < 0.05), and immunoreactivity from 0.7 +/- 0.1 to 0.42 +/- 0.1 mg/l (P < 0.05). After termination of fat perfusion, gastric lipase secretion increased again, though not reaching preinhibitory concentrations. During the intraduodenal perfusion with fat the plasma concentrations of glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) increased from 6.9 +/- 0.5 to 15.1 +/- 1.5 pmol/l (P < 0.05) and from 1.2 +/- 0.4 to 3.8 +/- 0.9 pmol/l (P < 0.05). This study reveals a negative effect of fat in the duodenum on gastric lipase secretion. This effect may be mediated by GLP-1 and/or CCK.
Asunto(s)
Colecistoquinina/metabolismo , Duodeno/metabolismo , Grasas/metabolismo , Glucagón/metabolismo , Lipasa/antagonistas & inhibidores , Fragmentos de Péptidos/metabolismo , Precursores de Proteínas/metabolismo , Estómago/enzimología , Adulto , Femenino , Aceites de Pescado/metabolismo , Aceites de Pescado/farmacología , Ácido Gástrico/metabolismo , Gastrinas/sangre , Gastrinas/farmacología , Péptido 1 Similar al Glucagón , Humanos , Masculino , Valores de Referencia , Secretina/sangre , Estómago/efectos de los fármacosRESUMEN
BACKGROUND: Gastric lipase secretion is stimulated by gastrin in plasma, but its regulation by secretin is unknown. METHODS: In 7 normal persons we investigated the effect of exogenous secretin on the output of gastric lipase stimulated by intravenous gastrin-17. The gastric content was measured using a nasogastric tube for aspiration. The quantitative lipase secretion was measured by an enzyme-linked immunosorbant assay (ELISA) and the lipolytic activity by a kinetic assay. Plasma concentrations of secretin and gastrin were measured by radioimmunoassay. RESULTS: Gastric lipase secretion (the quantity as well as the lipolytic activity) was significantly stimulated by gastrin. In response to secretin infusion, the lipolytic activity increased as acid secretion decreased. CONCLUSION: Secretin in postprandial concentrations does not influence the quantitative gastric lipase secretion stimulated by gastrin, but it increases lipolytic activity due to inhibition of acid secretion.
Asunto(s)
Jugo Gástrico/enzimología , Mucosa Gástrica/efectos de los fármacos , Lipasa/metabolismo , Secretina/farmacología , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Mucosa Gástrica/metabolismo , Gastrinas/administración & dosificación , Gastrinas/sangre , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Radioinmunoensayo , Valores de Referencia , Secretina/sangreRESUMEN
The incretin and enterogastrone hormone, GLP-1, occurs in an amidated (GLP-1 (7-36) amide; 75%) and a glycine-extended (GLP-1 (7-37); 25%) form. Their effects on the endocrine pancreas are similar and their overall (mainly renal) elimination rates appear to equal. Assuming that they might differentially affect non-pancreatic targets we investigated the effect of GLP-1 (7-37) infused at 0.7 pmol/kg/min on sham-feeding induced acid secretion in six healthy volunteers. The infusion increased the plasma concentrations from 16+/-2 pmol/l to 45+/-2 pmol/l. This was associated with a 61+/-14% decrease in acid output compared to saline and was not significantly different from that previously observed with GLP-1 (7-36) amide infused at the same rate. We then compared the degradation of the two forms in human plasma at 37 degrees C in vitro. T1/2 values were 32+/-3 (7-37) and 42+/-2 min (7-36) amide (P=0.007). The difference in metabolism persisted after addition of diprotin A, an inhibitor of dipeptidyl peptidase IV, the enzyme responsible for the initial degradation of GLP-1 in plasma, and broader enzyme inhibitors. Thus, the only effect of the amidation of GLP-1 seems to be to enhance its survival in plasma.
Asunto(s)
Glucagón/sangre , Fragmentos de Péptidos/sangre , Precursores de Proteínas/sangre , Estómago/efectos de los fármacos , Adulto , Bacitracina/farmacología , Femenino , Ácido Gástrico/metabolismo , Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Humanos , Masculino , Persona de Mediana Edad , Oligopéptidos/farmacologíaRESUMEN
Glucagon-like peptide (GLP)-1 inhibits acid secretion and gastric emptying in humans, but the effect on acid secretion is lost after vagotomy. To elucidate the mechanism involved, we studied its effect on vagally stimulated gastropancreatic secretion and motility in urethan-anesthetized pigs with cut splanchnic nerves, in which insulin-induced hypoglycemia elicited a marked stimulation of gastropancreatic secretion and antral motility. In addition, we studied vagally stimulated motility and pancreatic secretion in isolated perfused preparations of the porcine antrum and pancreas. GLP-1 infusion (2 pmol. kg-1. min-1) strongly and significantly inhibited hypoglycemia-induced antral motility, gastric acid secretion, pancreatic bicarbonate and protein secretion, and pancreatic polypeptide (PP) secretion. GLP-1 (at 10(-10)-10(-8) mol/l) did not inhibit vagally induced antral motility, pancreatic exocrine secretion, or gastrin and PP secretion in isolated perfused antrum and pancreas. We conclude that the inhibitory effect of peripheral GLP-1 on upper gastrointestinal secretion and motility is exerted via interaction with centers in the brain or afferent neural pathways relaying to the vagal motor nuclei.
Asunto(s)
Motilidad Gastrointestinal/fisiología , Glucagón/farmacología , Páncreas/metabolismo , Jugo Pancreático/metabolismo , Sistema Nervioso Parasimpático/fisiología , Fragmentos de Péptidos/farmacología , Precursores de Proteínas/farmacología , Estómago/fisiología , Nervio Vago/fisiología , Animales , Bicarbonatos/metabolismo , Glucemia/metabolismo , Ácido Gástrico/metabolismo , Gastrinas/metabolismo , Motilidad Gastrointestinal/efectos de los fármacos , Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Humanos , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/inervación , Músculo Liso/fisiología , Neurotransmisores/farmacología , Páncreas/efectos de los fármacos , Páncreas/inervación , Jugo Pancreático/efectos de los fármacos , Polipéptido Pancreático/metabolismo , Sistema Nervioso Parasimpático/efectos de los fármacos , Estómago/efectos de los fármacos , Estómago/inervación , Porcinos , Vagotomía , Nervio Vago/efectos de los fármacosRESUMEN
BACKGROUND: Glucagon-like peptide-2 is formed from proglucagon in the intestinal L-cells and is secreted postprandially in parallel with the insulinotropic hormone GLP-1 (glucagon-like peptide-1), which in addition acts to inhibit gastric motility (enterogastrone effect) by inhibiting central parasympathetic outflow. GLP-2 has no effect on the endocrine pancreas. We here tested the hypothesis that GLP-2 acts as an enterogastrone. METHODS: Fourteen anesthetized pigs with their splanchnic nerves cut were subjected to insulin hypoglycemia, and force transducers were sutured to the antrum to record motility. GLP-2 was infused intravenously in doses from 1 to 6 pmol/kg/min after the onset of antral motility in response to hypoglycemia. RESULTS: Insulin hypoglycemia invariably and greatly increased the frequency and amplitude of antral phasic contractions. Infusions of GLP-2 dose dependently (1-6 pmol/kg/min) inhibited antral motility. At 2 pmol/kg/min, resulting in plasma GLP-2 concentrations of 102.5+/-19 pmol/l (normal postprandial range, 30-82 pmol/l), the motility index was inhibited by 91%+/-14%. CONCLUSIONS: Both of the intestinal glucagon-like peptides may operate as hormonal transmitters of the ileal brake effect.
Asunto(s)
Vaciamiento Gástrico , Hormonas Gastrointestinales/fisiología , Péptidos/fisiología , Periodo Posprandial , Antro Pilórico/fisiología , Animales , Hormonas Gastrointestinales/administración & dosificación , Péptido 1 Similar al Glucagón , Péptido 2 Similar al Glucagón , Hipoglucemia/fisiopatología , Péptidos/administración & dosificación , Antro Pilórico/fisiopatología , PorcinosRESUMEN
In plasma, glucagon-like peptide-1 7-36 amide (GLP-1) is rapidly degraded from the N terminus, generating the endogenous metabolite GLP-1 9-36 amide. This cleavage of GLP-1 eliminates its incretin effect, and the metabolite even may act as an antagonist. We have shown previously that GLP-1 strongly inhibited cephalic-induced antral motility in pigs. We decided, therefore, to examine the effect of GLP-1 9-36 amide, with and without GLP-1, on cephalic-induced motility in pigs. In one series of experiments, we studied the effect of three different doses of GLP-1 9-36 amide (2, 4, and 10 pmol/kg/min) on insulin-induced (hypoglycemia) antral motility in anaesthetized pigs (n = 9). In another series, we studied the effect of infusion of GLP-1 9-36 amide in two different doses (1 and 5 pmol/kg/min) in six pigs in which the antral motility was inhibited by GLP-1 7-36 amide in a dose of 2 pmol/kg/min. Plasma levels of intact GLP-1 7-36 amide and GLP-1 9-36 amide were determined using specific radioimmunoassays. Insulin-induced hypoglycemia increased the antral motility index from 0.4 +/- 0.1 to 8.3 +/- 3.5 (cm/min). The motility was constant throughout the experimental period and was absolutely unaffected by the infusion of GLP-1 9-36 amide at 10 pmol/kg/min, which resulted in a plasma concentration of 351 +/- 60 pmol/l. The inhibitory effect of GLP-1 7-36 amide on antral motility was reduced from 93 +/- 3% to 33 +/- 9% (p < 0.05) by concomitant infusion of GLP-1 9-36 amide in a dose of 5 pmol/kg/min. The metabolite GLP-1 9-36 amide has no effect on antral motility in pigs but is able to antagonize the inhibitory effect of GLP-1. Thus, an intact N terminus is essential for the gastrointestinal actions of GLP-1. Its primary metabolite may act as an endogenous antagonist.
Asunto(s)
Hormonas Gastrointestinales/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Péptidos/farmacología , Animales , Relación Dosis-Respuesta a Droga , Glucagón , Péptido 1 Similar al Glucagón/análogos & derivados , Péptidos Similares al Glucagón , Hipoglucemia/inducido químicamente , Fragmentos de Péptidos/antagonistas & inhibidores , Fragmentos de Péptidos/metabolismo , Antro Pilórico , PorcinosRESUMEN
Glucagon-like peptide-1 (GLP-1) may be one of the enterogastrone hormones of the ileal brake mechanism. We therefore studied its effects on gastric lipase secretion in healthy volunteers and vagotomized patients during infusion of pentagastrin. The intestinal incretin hormone GLP-1 (glucagon-like peptide-1, 7-36 amide) was investigated because of its inhibitory effects on gastric acid secretion and motility. GLP-1 infused intravenously in amounts corresponding to the postprandial release significantly inhibited pentagastrin-stimulated gastric lipase secretion and lipolytic activity. The inhibitory effect of GLP-1 persisted in vagotomized patients, suggesting that fundic chief cells, from which gastric lipase is released, or neighboring inhibitory cells could be equipped with GLP-1 receptors. Vagotomized patients had significantly higher plasma concentrations of gastrin and secretin. No significant changes of gastrin, secretin, and CCK secretion were seen during GLP-1 infusion in the vagotomized patients, whereas secretin decreased significantly in the healthy volunteers. GLP-1 seems to be a naturally occurring inhibitor of gastric lipase secretion acting via a nonvagal mechanism. Our results indicate that gastric lipase secretion is subject to hormonal stimulatory as well as inhibitory mechanisms.
Asunto(s)
Mucosa Gástrica/enzimología , Glucagón/farmacología , Lipasa/antagonistas & inhibidores , Fragmentos de Péptidos/farmacología , Precursores de Proteínas/farmacología , Anciano , Estudios de Casos y Controles , Femenino , Ácido Gástrico/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Péptido 1 Similar al Glucagón , Humanos , Infusiones Intravenosas , Lipasa/metabolismo , Masculino , Persona de Mediana Edad , Pentagastrina/farmacología , Estimulación Química , VagotomíaRESUMEN
BACKGROUND: Cancer of the oesophagus and the cardia tends to present late. Palliation of dysphagia is the prospect of most of the patients. This paper reports the use of argon electrocoagulation in 83 patients with inoperable cancer strictures in the oesophagus and cardia. METHODS: The argon electrocoagulation was done by a fibre conducting electricity and argon air to the site of coagulation. After treatment the patients were allowed to take fluids and normal food the same evening or the next morning. After recanalization the patients were treated regularly every 3-4 weeks. RESULTS: Recanalization enabling passage for normal food was achieved with 1 treatment in 48 patients (58%), whereas 22 (26%) needed more than 1 treatment. In 13 patients (16%) the ability to eat normal food was not achieved. In these patients dysphagia improved at least one grade. Perforation was seen in seven patients (8%) and in 1% of treatments. Perforations were successfully treated conservatively in six of the seven patients. Sixty-three patients (76%) died during the investigation period, on average 146 days (range, 43-397 days) after diagnosis. CONCLUSION: Argon electrocoagulation offers an easy, cheap, and safe alternative to treatment with laser photocoagulation and expandable metal stents.
Asunto(s)
Electrocoagulación/métodos , Neoplasias Esofágicas/terapia , Esofagoscopía , Gastroscopía , Cuidados Paliativos/métodos , Neoplasias Gástricas/terapia , Anciano , Cardias , Trastornos de Deglución/terapia , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: Gastric lipase and gastric acid are secreted simultaneously. The aim of this study was to investigate whether the acid interferes with the lipase secretion. The secretion of human gastric lipase was studied during blockade of gastric acid secretion and modified sham feeding to estimate the impact of these conditions on both gastric lipase enzyme activity and immunoreactivity. METHODS: Eight healthy volunteers were intubated with a nasogastric tube. We examined gastric aspirates for the amount and activity of lipase secretion during basal conditions, after blockade of acid secretion with a proton pump inhibitor (omeprazole iv. infusion), and in response to sham feeding (chewing gum) during the blockade. RESULTS: The amount of secreted gastric lipase was unaffected by blockade of acid secretion and increased significantly after sham feeding (169.9+/-35.7 microg/15 min to 348.1+/-79.2 microg/15 min; p < 0.01). Likewise, the output of enzyme activity increased after sham feeding (0.63+/-0.09 kU/15 min to 1.52+/-0.36 kU/15 min; p < 0.03). The concentration of enzyme activity remained unchanged by blockade of acid secretion, whereas the output of enzyme activity was decreased, probably because of reduced volume secretion or denaturation and conformational changes of the enzyme. Plasma concentrations of gastrin increased in response to blockade of acid secretion (basal 9.6+/-1.4 pmol/L to 13.3+/-2.9 pmol/L; p < 0.02). CONCLUSIONS: Gastric acid secretion is not a prerequisite for gastric lipase secretion. Lipase enzyme activity, though, is sensitive to anacidic conditions.
Asunto(s)
Ingestión de Alimentos/fisiología , Ácido Gástrico/metabolismo , Lipasa/metabolismo , Estómago/enzimología , Adulto , Femenino , Gastrinas/sangre , Humanos , Masculino , Omeprazol/farmacología , Inhibidores de la Bomba de ProtonesRESUMEN
Surgery in the lithotomy position can provoke ischaemic lesions in the lower leg. We assessed lower leg oxygen saturation using near-infrared spectroscopy (NIRS) in 42 patients undergoing urinary tract surgery. Lower leg perfusion pressure was calculated as the difference of mean arterial pressure to pressure in an air bag supporting the lower leg and the hydrostatic pressure difference from the level of the lower leg to the heart. During elevation of the lower leg for 25 (3-65) min (median and range), mean arterial pressure decreased from 100 (73-125) to 77 (53-112) mmHg and the lower leg perfusion pressure dropped from 103 (80-122) to 21 (-6-65) mmHg, corresponding to a reduction in oxygen saturation of the medial gastrocnemius muscle from 68% (40-100%) to 58% (20-96%) (P < 0.01). The results demonstrate significant desaturation of the calf muscles during surgery in the lithomy position.
Asunto(s)
Síndromes Compartimentales/etiología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Oxígeno/metabolismo , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Anciano de 80 o más Años , Presión Sanguínea , Síndromes Compartimentales/metabolismo , Femenino , Humanos , Presión Hidrostática , Isquemia/etiología , Isquemia/metabolismo , Pierna/irrigación sanguínea , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Complicaciones Posoperatorias/metabolismo , Postura , Espectroscopía Infrarroja Corta , Factores de TiempoRESUMEN
BACKGROUND: Glucagon-like peptide-1 (GLP-1)(7-36) amide is an intestinal incretin hormone which also inhibits gastric acid secretion in humans. Its mechanism of action is unclear, but it strongly inhibits vagally induced secretion (sham feeding), suggesting that it could influence vagal activity. AIM/METHODS: The effect of intravenous GLP-1 (7-36 amide) (1 pmol/kg/min) was studied on pentagastrin induced acid secretion in otherwise healthy subjects, previously vagotomised for duodenal ulcer (n = 8) and in a group of young (n = 8) and old (n = 6) healthy volunteers. RESULTS: Pentagastrin increased acid secretion significantly in all three groups, but the plateau concentration in the vagotomised subjects was lower than in controls. Infusion of GLP-1 (7-36 amide) significantly inhibited acid secretion in the control groups (to 67 (SEM 6) and 74 (SEM 3)% of plateau concentrations in young and old controls, respectively) but had no effect in the vagotomised subjects. Differences in plasma concentrations of GLP-1 (7-36 amide), recovery of gastric marker, duodenal regurgitation, or Helicobacter pylori status could not explain the lack of effect. Blood glucose was lowered equally by GLP-1 (7-36 amide) in all subjects. CONCLUSION: The inhibitory effect of GLP-1 (7-36 amide) on acid secretion depends on intact vagal innervation of the stomach.
Asunto(s)
Úlcera Duodenal/cirugía , Ácido Gástrico/metabolismo , Fragmentos de Péptidos/farmacología , Vagotomía , Adulto , Anciano , Glucemia/metabolismo , Úlcera Duodenal/sangre , Femenino , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Glucagón , Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Humanos , Masculino , Persona de Mediana Edad , Pentagastrina/farmacología , Fragmentos de Péptidos/sangreRESUMEN
Our purpose was to examine gastric lipase secretion after cephalic stimulation (sham feeding) and to examine the effect of cholinergic blockade. Eight healthy volunteers, four women and four men, age 21-58 years, were studied twice on separate days. They were sham fed with and without infusion of atropine. Gastric content was measured and the amount as well as the activity of gastric lipase output were determined. Plasma concentrations of gastrin, secretin, and cholecystokinin (CCK) were measured simultaneously by radioimmunoassays. Cephalic stimuli can evoke human gastric lipase secretion, and this effect was almost ablated by atropine blockade of cholinergic receptors. The concentrations of CCK and secretin in plasma were unaffected by sham feeding with or without atropine blockade, whereas gastrin was stimulated by sham feeding after atropine blockade. Gastric lipase secretion in man is apparently controlled by interacting vagal and hormonal mechanisms.
Asunto(s)
Atropina/farmacología , Mucosa Gástrica/enzimología , Lipasa/metabolismo , Antagonistas Muscarínicos/farmacología , Adulto , Colecistoquinina/sangre , Femenino , Alimentos , Gastrinas/sangre , Humanos , Masculino , Persona de Mediana Edad , Radioinmunoensayo , Secretina/sangreRESUMEN
BACKGROUND AND STUDY AIMS: Iatrogenic esophageal perforation during palliative endoscopic treatment in patients with incurable esophageal or cardiac cancer is a severe complication, associated with a high rate of mortality. The treatment remains controversial, since both nonsurgical and surgical treatment regimens are used. The present study describes a nonsurgical regimen. PATIENTS AND METHODS: Nine cases of perforation occurred in 142 consecutive patients referred for endoscopic palliation of dysphagia, corresponding to a perforation rate of 6%. Laser therapy was the main treatment used (argon plasma coagulation or Nd:YAG photocoagulation). RESULTS: Nonsurgical treatment was successful in six patients (75%). Two patients died (22%) as a direct result of esophageal perforation following endoscopic palliation procedures. CONCLUSION: These findings show an acceptable mortality rate using a nonsurgical treatment regimen involving broad-spectrum antibiotics, nasogastric suction, and parenteral nutrition, with pleural drainage and endoprosthesis placement in addition when indicated.
Asunto(s)
Dilatación/efectos adversos , Neoplasias Esofágicas/complicaciones , Perforación del Esófago/terapia , Estenosis Esofágica/terapia , Esofagoscopía/efectos adversos , Cuidados Paliativos , Anciano , Anciano de 80 o más Años , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Electrocoagulación , Neoplasias Esofágicas/terapia , Perforación del Esófago/etiología , Femenino , Humanos , Coagulación con Láser , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , StentsRESUMEN
BACKGROUND: Gastrin is an important stimulator of gastric lipase secretion in man. In advanced pancreatic insufficiency gastric lipases might compensate for the lack of pancreatic lipases, but the role of gastrin in such compensation remains to be evaluated. The aim of this study was to examine the effect of gastrin on the gastric lipase secretion in patients with pancreatic insufficiency. METHODS: Eight patients with pancreatic insufficiency secondary to alcohol abuse were studied, and six healthy subjects volunteered as controls for the study. All volunteers received identical doses of intravenous gastrin-17 (10, 30, and 60 pmol/kg/h). The gastric content was measured, using a nasogastric tube for aspiration, and the amount and activity of gastric lipase output were determined. Plasma concentrations of gastrin, secretin, and cholecystokinin were measured by radioimmunoassays. RESULTS: The increased plasma levels of gastrin were accompanied by a dose-dependent increase in the amount and activity of gastric lipase in controls, but in the patients the response was almost abolished. CONCLUSIONS: Gastrin in postprandial concentrations does not influence the secretion of gastric lipase in patients with pancreatic insufficiency due to chronic pancreatitis.
Asunto(s)
Insuficiencia Pancreática Exocrina/enzimología , Mucosa Gástrica/enzimología , Gastrinas/fisiología , Lipasa/biosíntesis , Adulto , Estudios de Casos y Controles , Colecistoquinina/sangre , Insuficiencia Pancreática Exocrina/etiología , Femenino , Gastrinas/sangre , Hormonas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis Alcohólica/complicaciones , Secretina/sangreRESUMEN
Surgical procedures necessitating the use of the lithotomy position can be associated with neuromuscular lesions, usually arising from compression of nerves and muscles. Compartment syndrome of the lower extremities is a grave complication which, if unrecognized, can lead to either permanent neuromuscular dysfunction or limb loss. We report two cases of compartment syndrome complicating surgery in the lithotomy position.