RESUMEN
OBJECTIVE: Impaired tubular esophageal motility is involved in the pathogenesis of gastroesophageal reflux disease, which, in turn, has been shown to cause nosocomial pneumonia in critically ill patients. As multiple factors are involved, this pilot study was undertaken to evaluate whether, similarly, impaired esophageal motility may contribute to nosocomial infections by determining esophageal motility in critically ill patients undergoing mechanical ventilation and sedation in comparison to that of a healthy control group. DESIGN: Open, single-centered study. PATIENTS AND METHODS: Fifteen consecutive ventilated intensive care unit (ICU) patients with different diseases and three regimens of analgo-sedation were included: group 1: no analgo-sedation, group 2: ketamine and benzodiazepines, and group 3: fentanyl and benzodiazepines. Six healthy volunteers were studied as controls. Twenty-four hour esophageal anterograde (propulsive) and retrograde motility changes were assessed by a manometry system. RESULTS: The frequencies of contractions were 0.67 +/- 0.1/min (no analgo-sedation) 0.093 +/- 0.02 (ketamine) and 0.076 +/- 0.01 (fentanyl) (p < 0.05 as compared to controls). The amplitudes (% of maximum) were 98 % (control), 58 % (analgo-sedation), 38 % (ketamine) and 42 % (fentanyl; p < 0.05 for the comparison of fentanyl and ketamine with controls). Whereas the percentage of propulsive contractions was significantly decreased in patients (no sedation: 45 %, ketamine: 34 %; fentanyl: 35 %, p < 0.05) as compared to controls (72 %), the percentage of retrograde contractions increased: no sedation: 29 %, ketamine: 34 % and fentanyl: 37 % as compared to controls: 10 %, p < 0.05. Analysis according to the underlying diseases showed marked inhibition of motility parameters within any disease group in comparison with controls. CONCLUSIONS: Irrespective of the underlying disease, propulsive motility of the esophageal body is significantly reduced during any kind of sedation in critically ill patients. Possibly central as well peripheral drug-related effects are involved in such a depression. Twenty-four hour motility recordings appear to be a valuable and feasible method to quantify and analyze esophageal motor disorders in critically ill patients.
Asunto(s)
Infección Hospitalaria/etiología , Trastornos de la Motilidad Esofágica/complicaciones , Trastornos de la Motilidad Esofágica/fisiopatología , Manometría , Monitoreo Fisiológico , Neumonía/etiología , Adulto , Anciano , Estudios de Casos y Controles , Sedación Consciente/efectos adversos , Enfermedad Crítica , Femenino , Motilidad Gastrointestinal , Humanos , Masculino , Manometría/métodos , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Proyectos Piloto , Respiración Artificial/efectos adversos , Factores de TiempoRESUMEN
In gastrointestinal smooth muscle, intracellular Cl- is maintained at levels higher than its electrochemical equilibrium. Therefore, Cl- efflux through receptor-mediated opening of Cl- channels should result in membrane depolarization and may be sufficient to activate voltage-sensitive calcium channels (VSCCs). To determine the contribution of Cl- channels to receptor-mediated contraction of the longitudinal muscle layer of the rabbit distal colon, we studied the mechanical response of muscle strips to substance P, carbachol and potassium depolarization following the depletion of Cl- i, and in the presence of the Cl- channel blocker 5-nitro-2-(3-phenylpropyl-amino)-benzoate (NPPB). A 60-min incubation of tissues in a HEPES-buffered solution in which NaCl had been replaced by Na isethionate (or Na gluconate) in equimolar amounts resulted in disappearance of phasic contractions, and in a partially reversible reduction of the tonic response to substance P and carbachol, but not to KCl depolarization. When the agonist was applied to tissues in control solution, or to Cl-(-)depleted tissues in a solution in which Na+ was acutely replaced in equimolar amounts by N-methyl-D-glucosamine, the mechanical response to substance P and carbachol was almost abolished. Acute Na+ replacement alone without prior Cl- depletion did not abolish phasic contractions, but reduced the tonic response to substance P and carbachol. Similar to the effect of Cl- depletion, incubation of tissues in NPPB (6.6 x 10(-5) M) reduced the tonic response to substance P and carbachol, and abolished phasic contractions. These findings are consistent with a contribution of a Cl- channel to the receptor-mediated activation of colonic smooth muscle. In addition, the data suggest that transient Cl- channel mediated depolarizations may play a role in the generation of phasic contractions.
Asunto(s)
Canales de Cloruro/fisiología , Colon/fisiología , Músculo Liso/fisiología , Receptores de Superficie Celular/fisiología , Animales , Canales de Cloruro/antagonistas & inhibidores , Cloruros/metabolismo , Colon/metabolismo , Espacio Extracelular/metabolismo , Femenino , Motilidad Gastrointestinal/efectos de los fármacos , Motilidad Gastrointestinal/fisiología , Técnicas In Vitro , Masculino , Músculo Liso/metabolismo , Nitrobenzoatos/farmacología , Conejos , Sodio/fisiologíaRESUMEN
To investigate the influence of the cholinergic nerves on the action of i.v. ethanol on interdigestive gastric acid, pancreatic enzyme, and bile acid output, seven healthy volunteers were studied. On each of 4 different days, they swallowed a multilumen intestinal tube system that allowed the measurement of intraluminal pressures and the collection of gastric and duodenal juice. The subjects received an i.v. infusion of either ethanol (600 mg/kg for 30 min followed by 3 mg/kg/min), atropine (5 mu/kg/h), a combination of both drugs, or NaCl. Whereas ethanol did not significantly influence motility, atropine induced motoric quiescence. Ethanol significantly (p less than 0.05) stimulated gastric acid output, by 55%, whereas atropine inhibited it by 91%. When ethanol and atropine were given together, gastric acid output was significantly higher than during atropine use alone. Both ethanol and atropine inhibited pancreatic amylase output--by 47% and by 82%, respectively. The degree of inhibition was 80% when ethanol and atropine were given simultaneously. Atropine but not ethanol significantly reduced bile acid output. The finding that atropine did not completely reverse the stimulating effect of i.v. ethanol on gastric acid secretion suggests that ethanol stimulates gastric acid secretion not only by a cholinergic but also by a noncholinergic mechanism. The observation that atropine did not reverse the inhibiting effect of ethanol suggests, but does not prove, that the effect of ethanol on the pancreas is predominantly mediated by cholinergic nerves.
Asunto(s)
Atropina/farmacología , Ácidos y Sales Biliares/metabolismo , Etanol/farmacología , Ácido Gástrico/metabolismo , Motilidad Gastrointestinal/efectos de los fármacos , Páncreas/enzimología , Sistema Nervioso Parasimpático/fisiología , Adulto , Amilasas/metabolismo , Etanol/sangre , Gastrinas/sangre , Humanos , Masculino , Páncreas/efectos de los fármacos , Polipéptido Pancreático/sangre , Estómago/efectos de los fármacosRESUMEN
To investigate the influence of beer on gastric and pancreatic secretion, 14 fasted volunteers were studied on two different days. A multilumen intestinal tube allowed measurement of intraluminal pressures and collection of gastric and duodenal juices. Seven subjects received in random order 250 ml of either beer or glucose (5.6%, w/v) intragastrically; seven other subjects received these intrajejunally. After 15 min, 48 +/- 8% of beer and 47 +/- 6% of glucose were emptied into the duodenum. Intragastric beer induced a nearly sevenfold increase in gastric acid output as compared with glucose (16.3 +/- 2.9 mmol/h versus 2.5 +/- 0.6 mmol/h; p less than 0.05), intrajejunal beer induced a nearly threefold increase (5.1 +/- 0.8 mmol/h versus 1.7 +/- 0.3 mmol/h). The stimulated gastric acid output was threefold higher after intragastric than after intrajejunal beer. Trypsin output was slightly but significantly (p less than 0.05) stimulated by intragastric beer as compared with glucose (4,639 +/- 460 U/h versus 3,628 +/- 399 U/h) and nearly threefold by intrajejunal beer (2,579 +/- 455 U/h versus 849 +/- 181 U/h) (p less than 0.05). Trypsin response to intragastric beer was 1.8 times higher than after intrajejunal beer (p less than 0.05). Intragastric beer induced a nearly ninefold increase of the 1 h integrated plasma gastrin response as compared with glucose (998 +/- 347 pM min vs 115 +/- 70 pM min) (p less than 0.05). Intrajejunal beer and glucose did not release gastrin. We conclude that both intragastric and intrajejunal beer stimulate gastric acid and pancreatic enzyme secretion; intragastric beer being a more potent stimulant. Gastrin might partially mediate the responses to intragastric but not to intrajejunal beer.
Asunto(s)
Cerveza , Ácido Gástrico/metabolismo , Yeyuno/fisiología , Páncreas/metabolismo , Estómago/fisiología , Adulto , Humanos , Masculino , Tripsina/metabolismoRESUMEN
UNLABELLED: The effects of the E2 prostaglandin nocloprost (9b-chloro-16,16-dimethyl-prostaglandin E2) on esophageal motility and acid clearance were evaluated in a double-blind placebo controlled study in six healthy volunteers. Motility of the tubular esophagus was measured by means of a low compliance perfusion system (four channels, recording ports 10 cm apart, the distal localized in the stomach). After eight hours fasting and a 60-minutes baseline measurement (with standardized swallowing of 5 cc water every three minutes) the volunteers swallowed on two separate days in randomized order either 200 micrograms nocloprost (solved in 50 cc water) or placebo. Then the motility of the tubular esophagus was assessed for another 60-minutes during standardized swallowing. Thereafter, the motility probe was removed and a pH-electrode placed 10 cm above the lower esophageal sphincter. In order to assess the esophageal clearance, four times 5 cc of 0.1 N HCl were infused into the esophagus 10 cm above the electrode and the time between the infusion of HCl and the increase of the pH above pH 4.0 measured. RESULTS: In five out of six volunteers the duration of esophageal contractions were decreased after administration of nocloprost as compared to placebo (6.23 +/- 1.2 vs. 5.80 +/- 1.1 seconds, p = 0.07). In contrast, neither propagation velocity, nor amplitude of contraction or acid clearance were significantly affected by nocloprost. CONCLUSIONS: These findings suggest that in healthy volunteers nocloprost changes the pattern of esophageal contractions (duration) without affecting amplitude, velocity of propagation or acid clearance.
Asunto(s)
Esófago/efectos de los fármacos , Determinación de la Acidez Gástrica , Prostaglandinas F Sintéticas/farmacología , Adulto , Deglución/efectos de los fármacos , Método Doble Ciego , Humanos , MasculinoRESUMEN
Patients on chronic hemodialysis often need blood transfusions due to erythropoietin deficiency. Even after successful kidney transplantation iron overload may persist. Former histological studies have revealed siderosis of the liver in 69% of all patients whose serum ferritin was above 1100 ng/ml. The aim of the present study was to evaluate the influence of iron overload on liver function. In 146 symptom free patients with renal allografts serum ferritin was determined to detect possible iron overload. Serum ferritin between 4 and 5480 ng/ml were found (women: 358.7 +/- 105.3; men 282.4 +/- 63.3 ng/ml; x +/- SEM). Twelve patients (8.1%) had ferritin levels higher than 1100 ng/ml. These twelve patients as well as another group of eight patients with renal allografts whose serum ferritin was known to be higher than 1100 ng/ml were included for further evaluation. Their data were matched and compared with those of a control group also patients with renal allograft (same age and sex) whose serum ferritin was lower than 1100 ng/ml. Transaminases (SGPT 22.6 +/- 3.6 vs. 15.4 +/- 6.0 U/l; SGOT 14.7 +/- 2.0 vs. 13.0 +/- 4.8 U/l) and plasma glucose (90.5 +/- 7.1 vs. 76.8 +/- 3.7 mg/dl) were found to be significantly higher (p less than 0.05) in patients with serum ferritin levels above 1100 ng/ml. Elevated transaminases were significantly more frequent in patients with high serum ferritin (9 vs. 2; p less than 0.02) as compared with the control. Ferritin levels significantly correlated with the number of preceding blood transfusions (p less than 0.002). Hbs-persistence was detected in six out of 20 patients with high ferritin levels but only in one out of 20 in the control group (p less than 0.05) whereas anti-Hbs prevalence was not different in the two groups. These data indicate that chronic iron overload should be considered as a possible cause of chronic liver disease in patients with renal allografts.
Asunto(s)
Ferritinas/sangre , Trasplante de Riñón , Hígado/metabolismo , Siderosis/sangre , Adolescente , Adulto , Glucemia/análisis , Femenino , Antígenos de Superficie de la Hepatitis B/análisis , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Diálisis Renal , Transaminasas/sangre , Reacción a la TransfusiónRESUMEN
Peptide YY has been shown to have stimulatory and inhibitory effects on gastrointestinal motility. However, the receptors mediating these effects are unknown. To determine if specific YY receptor agonists can mediate the effects on gastrointestinal motility we studied the effects of peptide YY (PYY), of Pro34PYY, a selective Y1 agonist, and of PYY 3-36, a selective Y2 agonist, on the motility in isolated smooth muscle strips from rabbit small and large intestine. In strips from distal colon, PYY stimulated spontaneous motility whereas it inhibited spontaneous contractions in circular strips from distal ileum. In distal circular colon maximal inotropic response (10.1 +/- 2.1% of a maximal response to carbachol 10(-5) M) was found at PYY 10(-8) M; (ED50 3.1 +/- 1.2 x 10(-9) M). In distal circular ileum maximal inhibition (by 39 +/- 20% of basal motility index) was found at 10(-7) M; (ID50 6.2 +/- 1.4 x 10(-9) M). PYY caused a dose-dependent inhibition of the on-contraction induced by electrical field stimulation. This inhibition could not be reversed by alpha- or beta-adrenergic blockade. PYY had no influence on the inotropic response evoked by carbachol. Both the stimulatory effect of PYY observed in distal colon and the inhibitory effect in distal ileum could be reproduced by the Y1 agonist Pro34PYY, but not by the Y2 agonist PYY 3-36. In distal circular colon the maximal inotropic response evoked by the Y1 agonist was 10 +/- 1.4%; (ED50 1.2 +/- 0.5 x 10(-8) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Motilidad Gastrointestinal/fisiología , Músculo Liso/fisiología , Péptidos/fisiología , Receptores de Neuropéptido Y/fisiología , Animales , Técnicas de Cultivo , Péptido YY , Conejos , Receptores de Neuropéptido Y/clasificaciónAsunto(s)
Anemia Perniciosa/patología , Enfermedades del Sistema Nervioso Autónomo/patología , Síndrome de Shy-Drager/patología , Encéfalo/patología , Diagnóstico Diferencial , Femenino , Mucosa Gástrica/patología , Humanos , Espectroscopía de Resonancia Magnética , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Hypercalcemia produced in healthy volunteers by intravenous infusions of calciumgluconolactobionate increased outputs of gastric acid, pepsin, and pancreatic enzymes. Hypercalcemia did not affect gallbladder emptying and serum gastrin values. Further, intravenous somatostatin (SRIF, 5 micrograms/kg.h) markedly inhibited secretion of gastric acid (p less than 0.01), pepsin (p less than 0.05), and pancreatic enzymes (p less than 0.02) stimulated by hypercalcemia. SRIF-inhibited outputs were below basal values. These results indicate that the inhibitory effect of SRIF on exocrine cells of the human gastrointestinal tract can not be reversed by extracellular hypercalcemia.
Asunto(s)
Jugo Gástrico/metabolismo , Hipercalcemia/fisiopatología , Lipasa/metabolismo , Páncreas/efectos de los fármacos , Somatostatina/farmacología , Tripsina/metabolismo , Adolescente , Adulto , Calcio/sangre , Femenino , Ácido Gástrico/metabolismo , Gastrinas/sangre , Humanos , Masculino , Páncreas/metabolismo , Pepsina A/metabolismoRESUMEN
BACKGROUND: It is well established that a 7-day triple therapy achieves eradication rates of Helicobacter pylori between 90% and 95%. Due to a lack of highly effective short-term eradication studies the aim of the present pilot study was to investigate the effect of a 4-day triple therapy with the new proton pump inhibitor rabeprazole (20 mg b. i. d.) in combination with clarithromycin (500 mg b. i. d.) and amoxicillin (1 g b. i. d.) without acid-suppressive pre-treatment in patients with H. pylori-related peptic ulcer disease. METHODS: 20 patients (11 men, 9 women) with endoscopically diagnosed peptic ulcers (gastric ulcer: n = 5; duodenal ulcer: n = 9; combined gastric and duodenal ulcer: n = 2, gastric or duodenal ulcer scars: n = 4) and H. pylori infection were consecutively recruited. The Helicobacter pylori status was assessed by means of histology, CLO (urea-) test and C13-urea breath test (C13-UBT) at entry. Treatment success was determined by C13-UBT 35-42 days after end of treatment. RESULTS: In 18 out of the 20 patients (90%) [77-100%, 95%-CI] a negative test result was found in C13-UBT 35-42 days after treatment. The 2 patients who remained H. pylori-positive had a duodenal ulcer. CONCLUSION: A 4-day triple therapy of rabeprazole in combination with clarithromycin and amoxicillin seems to be highly effective in eradicating H. pylori and well tolerated in patients with gastric and duodenal ulcer disease. The achieved eradication rate of 90% is comparable with the established 7-day triple therapy regimens. On the basis of these results and considering costs, side effects and compliance a large number of patients should be enrolled in a confirmatory 4-day eradication trial.
Asunto(s)
Amoxicilina/administración & dosificación , Antiulcerosos/administración & dosificación , Bencimidazoles/administración & dosificación , Claritromicina/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Úlcera Péptica/tratamiento farmacológico , 2-Piridinilmetilsulfinilbencimidazoles , Adulto , Anciano , Amoxicilina/efectos adversos , Antiulcerosos/efectos adversos , Bencimidazoles/efectos adversos , Claritromicina/efectos adversos , Esquema de Medicación , Quimioterapia Combinada , Femenino , Helicobacter pylori/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/análogos & derivados , Proyectos Piloto , RabeprazolRESUMEN
BACKGROUND: Tubeless pancreatic function tests measuring the content of elastase-1 and the activity of chymotrypsin in stool are used with different cut-off levels and with varying success in diagnosing functional impairment of the pancreas. The aim of our study was to re-evaluate the sensitivity and specificity of elastase-1 and chymotrypsin in stool in the assessment of exocrine pancreatic insufficiency. METHODS: In 127 patients displaying clinical signs of malassimilation, the secretin-caerulein test ('gold standard'), fecal fat analysis, fecal chymotrypsin activity and fecal elastase-1 concentration were performed. Exocrine pancreatic insufficiency was graded, according to the results of the secretin-caerulein test, into mild, moderate and severe. Chymotrypsin and elastase-1 in stool were estimated using two commercially available test kits. Fecal elastase-1 concentration of 200 and 100 microg/g stool and chymotrypsin activity of 6 and 3 U/g stool were used separately as cut-off levels for calculation. RESULTS: 1) In 65 patients, a normal pancreatic function was found using the secretin-caerulein test. In 62 patients, an exocrine pancreatic insufficiency was found and classified into severe (n = 25), moderate (n = 14) and mild (n = 23). 2) The correlation between fecal elastase-1 and chymotrypsin with duodenal enzyme outputs of amylase, lipase, trypsin, chymotrypsin and elastase-1 ranged between 33% and 55% and 25% and 38%, respectively. 3) Using a cut-off of 200 microg elastase-1/g, stool sensitivities of fecal elastase-1 and fecal chymotrypsin (cut-off: 6 U/g) were 100% and 76%, respectively (P < 0.0001 and P < 0.001 respectively) in severe exocrine pancreatic insufficiency, 89% and 47% respectively (P < 0.001; P = 0.34, respectively) in moderate and 65% for both in mild pancreatic insufficiency. Specificities of elastase-1 and chymotrypsin in stool were 55% and 47%, respectively. 4) Elastase-1 based diagnostic provided a positive predictive value of 50% using a cut-off' 200 microg/g stool in a representative group of consecutively recruited patients with gastroenterological disorders. CONCLUSION: Determination of fecal elastase-1 is highly sensitive in the diagnosis of severe and moderate exocrine pancreatic insufficiency and is of significantly higher sensitivity than fecal chymotrypsin estimation. Specificity for both stool tests is low. Correlation between elastase-1 and chymotrypsin in stool and duodenal enzyme outputs is moderate. Neither test is suitable for screening, as they provide a pathologic result in roughly half of 'non-pancreas' patients.
Asunto(s)
Insuficiencia Pancreática Exocrina/diagnóstico , Heces/enzimología , Elastasa Pancreática/análisis , Pruebas de Función Pancreática , Biomarcadores/análisis , Ceruletida , Quimotripsina/análisis , Insuficiencia Pancreática Exocrina/enzimología , Humanos , Modelos Logísticos , Pruebas de Función Pancreática/métodos , Secretina , Sensibilidad y EspecificidadRESUMEN
BACKGROUND AND STUDY AIMS: The action of ethanol and alcoholic beverages on the gastric mucosa in healthy humans is largely unknown. This study was designed to compare the effects of beer, white wine, whisky, and the comparable pure ethanol solutions on the gastric and duodenal mucosa in a controlled, randomized, double-blind endoscopic investigation. MATERIALS AND METHODS: In 47 healthy human volunteers, 100 ml of beer, or white wine, or whisky, or a comparable pure ethanol solution (4%, 10%, 40% vol/vol), or isotonic saline as a control, were sprayed on the antral mucosa. The endoscopic appearance of the gastric and duodenal mucosa was assessed before, immediately after, and 30, 60, 240 minutes and 24 hours after instillation. The lesions were scored using an endoscopic grading system (0-5; 0 = normal mucosa and 5 = ten or more hemorrhagic lesions). RESULTS: Pure ethanol damaged the gastric mucosa in a dose-dependent fashion. The lesions occurred within 30 minutes, and reached a maximum after 60 minutes (antral score for 4% = 1.3; 10% = 1.8; 40% 3.8; control = 1.5). Beer, wine and whisky also induced gastric mucosal injury, but to a lesser extent than the comparable ethanol solutions. The 24-hour integrated endoscopic scores for beer and wine were significantly lower (P < 0.05) than the corresponding ethanol content. In the case of pure ethanol > 10% and whisky, the lesions were still present 24 hours later (antral score for 10% = 1.5; 40% = 2.0; whisky = 2.3; control = 0). No lesions were observed in the duodenum. None of the volunteers reported any abdominal pain during the whole investigation. CONCLUSIONS: Intragastric application of 4%, 10%, and 40% vol/vol pure ethanol induces gastric, but not duodenal, mucosal lesions in a dose-dependent fashion. Beer, white wine, and whisky induce gastric mucosal lesions to a lesser degree than the corresponding ethanol content. Lesions induced by higher ethanol concentrations (> 10%) and whisky take more than 24 hours to heal. The lesser damage caused by alcoholic beverages may be due to the protective action of unknown nonalcoholic ingredients.
Asunto(s)
Bebidas Alcohólicas/toxicidad , Etanol/toxicidad , Mucosa Gástrica/efectos de los fármacos , Gastroscopía , Adulto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Mucosa Gástrica/patología , Humanos , MasculinoRESUMEN
We present the case of a 57-year-old woman who developed persistent jaundice and cholestasis four weeks after a severe burn injury (34% of the body surface, 19% second degree, 15% third degree). In the endoscopic retrograde cholangiography four months later the characteristic picture of sclerosing cholangitis was found. A causal relation between the thermal injury and the development of sclerosing cholangitis is likely because of this coincidence and the absence of any preexisting disease, especially of the hepatobiliary system. Other cholestatic liver disease could be excluded. Possible pathogenetic mechanisms are discussed, especially the increased permeability of the gut mucosa after burn injuries with consecutive translocation of bacteria and toxins and their transport into the biliary tract.
Asunto(s)
Quemaduras/complicaciones , Colangitis Esclerosante/etiología , Conductos Biliares Intrahepáticos/patología , Quemaduras/patología , Colangiopancreatografia Retrógrada Endoscópica , Colangitis Esclerosante/patología , Diagnóstico Diferencial , Femenino , Humanos , Hígado/patología , Pruebas de Función Hepática , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Granulocytic sarcomas (so-called chloromas) are rare extramedullary tumorlike proliferates of myelogenous precursor cells that may de novo precede acute leukemia or coincide with the first manifestation or relapse of acute myeloid leukemia. Rarely, such tumors represent the initial manifestation of a blast crisis in the course of a chronic myeloproliferative disease, such as chronic myeloid leukemia. If they occur in aleukemic patients incorrect diagnoses may result. Differential diagnostic considerations are being discussed by presenting the case of a 58-year-old man who experienced spinal cord compression by an isolated epidural mass lesion.
Asunto(s)
Leucemia Mieloide/patología , Compresión de la Médula Espinal/etiología , Biopsia , Crisis Blástica , Diagnóstico Diferencial , Humanos , Leucemia Mieloide/diagnóstico , Antígenos Comunes de Leucocito/análisis , Masculino , Persona de Mediana Edad , Compresión de la Médula Espinal/patología , Compresión de la Médula Espinal/cirugíaRESUMEN
To investigate the effect of aclatonium napadisilate (Ac), a synthetic cholinergic compound, on human interdigestive gastrointestinal function, six healthy volunteers underwent gastrointestinal intubation for measurement of duodeno-jejunal motor activity and pancreatic enzyme secretion. Each subject was studied twice on two separate days and received either aclatonium (300 mg) or placebo intraduodenally in randomized order. Aclatonium significantly increased the overall length of the cycle of interdigestive motor complex (IMC) by a mean of 34% (p less than 0.05) without stimulating the phases of increased motor activity. Aclatonium slightly, but significantly increased output of lipase during phase II of the IMC (p less than 0.05), whereas outputs during phase I and III were not significantly changed. We conclude that aclatonium in a dose of 300 mg has only weak cholinergic effects on motility and exocrine pancreatic secretion in healthy humans during the interdigestive state.
Asunto(s)
Acetilcolina/análogos & derivados , Amilasas/metabolismo , Motilidad Gastrointestinal/efectos de los fármacos , Lipasa/metabolismo , Páncreas/enzimología , Parasimpaticomiméticos/farmacología , Acetilcolina/farmacología , Adulto , Duodeno/efectos de los fármacos , Duodeno/fisiología , Femenino , Humanos , Yeyuno/efectos de los fármacos , Yeyuno/fisiología , Masculino , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Páncreas/efectos de los fármacos , Distribución Aleatoria , Valores de ReferenciaRESUMEN
BACKGROUND: Most patients with alcohol induced cirrhosis (AC) and chronic endotoxinaemia are not suffering from clinically evident systemic inflammatory reactions. This may be due to altered gene expression of cytokines, possibly related to endotoxin (for example, tolerance and sensitisation). Interleukin 18 (IL-18; interleukin gamma inducing factor) modulates local cytokine production in response to endotoxin (lipopolysaccharide (LPS)). AIM: To investigate the systemic immune response of patients with AC and to see if unstimulated peripheral blood mononuclear cells (PBMC) from patients with AC are activated and contribute to gene expression of IL-18. METHODS: Plasma levels of endotoxin (LPS) and serum levels of IL-18 were measured by enzyme linked immunoassay and the amoebocyte lysate test in 74 abstinent patients with different stages of AC (Child-Pugh stage A, n=18; B, n=22; C, n=34) and compared with healthy controls (n=43). Gene expression of IL-18 was assessed by semiquantitative reverse transcription-polymerase chain reaction in freshly isolated unstimulated PBMC of a subgroup of 14 patients with AC compared with five healthy controls. RESULTS: Gene expression of IL-18 specific mRNA in unstimulated PBMC was significantly enhanced in patients with advanced AC (Child-Pugh stage C) and correlated with plasma LPS and serum CD14 levels (Spearman rank correlation factors r=0.76 and r=0.72). Serum concentrations of IL-18 were also elevated compared with healthy controls (p<0.001) but correlation with serum levels of CD14 and plasma levels of LPS was much weaker compared with mRNA data (Spearman rank correlation factors r=0.47 and r=0.26). CONCLUSIONS: Our in vivo data suggest a presensitisation of "unstimulated" PBMC in the circulation of patients with AC by endotoxin. The term "unstimulated" may be inadequate in patients with AC. Further investigations are needed to define the exact mechanisms and localisation of sensitisation of PBMC in vivo.
Asunto(s)
Interleucina-18/metabolismo , Leucocitos Mononucleares/metabolismo , Cirrosis Hepática Alcohólica/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Expresión Génica , Humanos , Receptores de Lipopolisacáridos/sangre , Lipopolisacáridos/sangre , Masculino , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estadísticas no ParamétricasRESUMEN
The clinical and laboratory findings in seven female patients with primary autoimmune diseases, one female patient with lymphoplasmacytoid (LP) immunocytoma and IgM paraproteinemia, and two male patients with multiple myeloma are described. The common denominator in all patients was a lupus anticoagulant or a closely related coagulation disorder. Recurrent thrombosis was observed in six patients with autoimmune diseases and in two patients with malignant monoclonal gammopathies. Other clinical manifestations included cerebral disorders (four patients with autoimmune disease/two patients with monoclonal gammopathy), repeated obstetric complications (6/1), asymptomatic valvular heart disease (6/1), renal dysfunction (6/2), hepatic involvement (2/2), and arthropathy (2/0). Laboratory investigations revealed a biologic false-positive serological test for syphilis in six patients with autoimmune disease and one with monoclonal gammopathy, antinuclear antibodies (4/0), antibodies against DNA (4/1), and a positive direct Coombs test (3/1) which was accompanied by hemolytic anemia in two patients (1/1). Additionally slight leukocytopenia (2/1) and thrombocytopenia (6/2) were observed; abnormal bleeding was only seen in one patient with severe thrombocytopenia. Other complications characteristic of LP immunocytoma or multiple myeloma were missing. The obvious similarities between the patients with autoimmune diseases and the patients with malignant monoclonal gammopathies suggest analogous pathogenetic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)