Asunto(s)
Obstrucción de la Salida Gástrica/cirugía , Gastroplastia , Gastroscopía , Terapia por Láser/instrumentación , Polipropilenos , Complicaciones Posoperatorias/cirugía , Mallas Quirúrgicas , Femenino , Obstrucción de la Salida Gástrica/etiología , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , ReoperaciónRESUMEN
BACKGROUND: Several lines of evidence have led us to postulate that afferent vagal hyperactivity could be an important factor in the pathophysiology of the eating disorder bulimia nervosa. Ondansetron is a peripherally active antagonist of the serotonin receptor 5-HT3, and is marketed for prevention of vagally-mediated emesis caused by cancer chemotherapeutic agents. We investigated the effects of ondansetron on bulimic behaviours in patients with severe and chronic bulimia nervosa in a randomised, double-blind, placebo-controlled study. METHODS: We enrolled patients with severe bulimia nervosa (at least seven coupled binge/vomit episodes per week). The patients were otherwise healthy, their weight was normal, and they were not receiving medical or psychiatric treatment. During the first week of the study, patients recorded all eating-behaviour events to establish a baseline. In the second week, all patients received placebo, but were told that they were receiving either placebo or active drug. At the end of this single-blind phase, patients were randomly assigned placebo or ondansetron (24 mg daily) for a further 4 weeks. The primary outcome measure was the number of binge/vomit episodes per week. Data were analysed by intention to treat. FINDINGS: 29 patients met the inclusion criteria, of whom 28 completed the baseline study, and 26 completed the single-blind placebo week. 12 patients were assigned placebo, and 14 ondansetron; one patient in the ondansetron group dropped out owing to accidental injury. During the 4th week of double-blind treatment, mean binge/vomit frequencies were 13.2 per week (SD 11.6) in the placebo group, versus 6.5 per week (3.9) in the ondansetron group (estimated difference 6.8 [95% CI 4.0-9.5]; p<0.0001). The ondansetron group also showed significant improvement, compared with the placebo group, in two secondary indicators of disease severity. The amount of time spent engaging in bulimic behaviours was decreased on average by 7.6 h per week in the ondansetron group, compared with 2.3 h in the placebo group (estimated difference 5.1 [0.6-9.7]). Similarly, the number of normal meals and snacks increased on average by 4.3 normal eating episodes without vomiting per week in the ondansetron group, compared with 0.2 in the placebo group (estimated difference 4.1 [1.0-7.2]). INTERPRETATION: The decrease in binge-eating and vomiting under ondansetron treatment was not achieved by compensatory changes in eating behaviour such as by a smaller number of binges of longer duration, or by not eating, or by binge-eating without vomiting. Instead, our findings indicate a normalisation of the physiological mechanism(s) controlling meal termination and satiation. Since meal termination and satiety are mainly vagally mediated functions, since binge-eating and vomiting produce intense stimulation of vagal afferent fibres, and since ondansetron and other 5-HT3 antagonists decrease afferent vagal activity, the symptom improvement may result from a pharmacological correction of abnormal vagal neurotransmission.
Asunto(s)
Antieméticos/uso terapéutico , Bulimia/tratamiento farmacológico , Ondansetrón/uso terapéutico , Antagonistas de la Serotonina/uso terapéutico , Nervio Vago/efectos de los fármacos , Adolescente , Adulto , Vías Aferentes/efectos de los fármacos , Vías Aferentes/fisiopatología , Antieméticos/efectos adversos , Bulimia/fisiopatología , Método Doble Ciego , Conducta Alimentaria/efectos de los fármacos , Conducta Alimentaria/fisiología , Femenino , Humanos , Persona de Mediana Edad , Ondansetrón/efectos adversos , Receptores de Serotonina/efectos de los fármacos , Receptores de Serotonina/fisiología , Respuesta de Saciedad/efectos de los fármacos , Respuesta de Saciedad/fisiología , Antagonistas de la Serotonina/efectos adversos , Nervio Vago/fisiopatologíaAsunto(s)
Bulimia/tratamiento farmacológico , Ondansetrón/uso terapéutico , Adulto , Bulimia/fisiopatología , Esquema de Medicación , Femenino , Humanos , Ondansetrón/administración & dosificación , Ondansetrón/farmacología , Transmisión Sináptica/efectos de los fármacos , Resultado del Tratamiento , Nervio Vago/fisiopatologíaRESUMEN
BACKGROUND: Symptomatic lymphoceles are not uncommon after kidney transplantations. Surgical marsupialization with internal drainage is the treatment of choice. However, laparoscopic drainage is reportedly as effective, with only minimal trauma. METHODS: We attempted 14 laparoscopic lymphocele drainages during a 3-year period and studied the indications and limitations, using intraoperative ultrasonography in all cases. RESULTS: Laparoscopic drainage was successful in only 9 (64%) of 14 patients. A conversion to open laparotomy was necessary in five patients; their lymphoceles were lateral and either posterior or inferior to the kidney. Two patients with initially successful laparoscopic drainage required conversion to open laparotomy 21 and 83 days later; their lymphoceles were inferior to the kidney. Laparoscopic drainage shortened the median hospital stay by 4 days versus open surgical drainage and by 7 days versus conversion. Hospital costs for laparoscopic drainage averaged $7400 less versus open drainage and $10,300 less versus conversion. CONCLUSIONS: In patients with symptomatic lymphoceles medial and either superior or anterior to the kidney, laparoscopic drainage under intraoperative ultrasonographic guidance is easy, safe, and effective. It decreases hospitalization, convalescence, and costs. In patients with symptomatic lymphoceles lateral and either posterior or inferior to the kidney, laparoscopic drainage may fail because of anatomic inaccessibility and technical impracticability.
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Drenaje/métodos , Enfermedades Renales/terapia , Trasplante de Riñón/efectos adversos , Linfocele/terapia , Adolescente , Adulto , Drenaje/economía , Femenino , Costos de Hospital , Humanos , Enfermedades Renales/diagnóstico por imagen , Enfermedades Renales/etiología , Laparoscopía , Tiempo de Internación/economía , Linfocele/diagnóstico por imagen , Linfocele/etiología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , UltrasonografíaRESUMEN
In 10 patients undergoing laparoscopic cholecystectomy, creation of pneumoperitoneum caused immediate venous hypertension and stasis in the lower extremities as measured by percutaneous catheter and duplex scanning. These changes disappeared after deflation. As measured by spirometry, significant reductions in forced vital capacity of 23% and forced expiratory volume in 1 second of 22% were present 24 hours after surgery, and plasma interleukin-6 levels rose to 18 pg/mL. The visual analogue scale of resting pain increased to a median value of 2.5 postoperatively. When compared with other studies of open cholecystectomy, our results showed fewer restrictions of ventilation, lower cytokine levels, and lower pain scores. The minimal soft tissue trauma and early ambulation after laparoscopic cholecystectomy may decrease the risk of thrombosis despite an acute episode of venous stasis.
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Colecistectomía Laparoscópica , Hemodinámica , Interleucina-6/sangre , Mecánica Respiratoria , Velocidad del Flujo Sanguíneo , Colecistectomía Laparoscópica/efectos adversos , Femenino , Vena Femoral/fisiología , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Pulso ArterialRESUMEN
Pyrolysis of tissue in a hypoxic environment can produce carbon monoxide. The atmosphere of the peritoneal cavity is rendered hypoxic during laparoscopic cholecystectomy by insufflation with 100% carbon dioxide. To determine whether carbon monoxide is produced by electrocautery of tissue during laparoscopic cholecystectomy, nine patients undergoing this procedure had the insufflation gas after use of electrocautery analyzed for carbon monoxide. Blood was analyzed for carboxyhemoglobin in these same patients to determine whether carbon monoxide was being absorbed in dangerous amounts. Carbon monoxide was present in the peritoneal cavity 5 min after use of electrocautery was initiated at a median concentration of 345 ppm (range 25-1600 ppm), and at the end of surgery at a concentration of 475 ppm (range 100-1900 ppm). This was well in excess of the 35 ppm upper limit for a 1-h exposure set by the Environmental Protection Agency. The carboxyhemoglobin concentrations (mean +/- SD) were the same at the beginning (1.3% +/- 0.7%), end (1.2% +/- 0.7%), and the day after surgery (1.1% +/- 0.6%). Although there was no evidence of significant absorption of carbon monoxide in these patients, care should be taken to scavenge the gases produced by cautery of tissues to avoid operating room contamination during laparoscopic surgery.
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Monóxido de Carbono , Colecistectomía Laparoscópica/efectos adversos , Colelitiasis/cirugía , Electrocoagulación/efectos adversos , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Intraoperative venous stasis may increase the risk for perioperative deep vein thrombosis and pulmonary embolism. To determine if abdominal insufflation during laparoscopic cholecystectomy causes venous stasis, eight patients undergoing this procedure had their left common femoral veins examined by a duplex scanner before and after abdominal insufflation; the veins then were examined again before and after deflation. The right femoral veins were catheterized to measure femoral venous pressures. Abdominal insufflation to 14 millimeters of mercury pressure increased femoral venous pressures (10.2 +/- 4.1 millimeters of mercury to 18.2 +/- 5.1 millimeters of mercury; p < 0.001) and slowed peak blood velocities (24.9 +/- 8.5 centimeters per second to 18.5 +/- 4.5 centimeters per second; p < 0.05) without changing the cross-sectional areas (1.1 +/- 0.4 centimeter squared to 1.2 +/- 1.5 centimeter squared; p = NS) of the common femoral veins. Insufflation also reduced or eliminated pulsatility in the common femoral veins in 75 percent of the patients, indicating that insufflation was causing partial proximal venous obstruction. After 80 +/- 21 minutes of surgery, these changes remained significant. Deflation of the abdomen restored normal venous pulsatility in all patients, reduced femoral venous pressures (18.5 +/- 5.2 millimeters of mercury to 12.2 +/- 9.8 millimeters of mercury; p < 0.001), increased the peak blood velocities (14.2 +/- 6.8 centimeters per second to 28.1 +/- 16 centimeters per second; p < 0.05) and decreased the cross-sectional areas (1.4 +/- 0.6 centimeters squared to 0.9 +/- 0.4 centimeters squared; p < 0.05) of the common femoral veins, indicating venous decompression had occurred. The results suggest abdominal insufflation causes venous stasis during laparoscopic cholecystectomies. Measures shown to reduce intraoperative venous stasis, such as pneumatic compressive stockings, may benefit patients undergoing these procedures.
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Colecistectomía Laparoscópica/efectos adversos , Insuflación/efectos adversos , Embolia Pulmonar/epidemiología , Insuficiencia Venosa/epidemiología , Adulto , Anciano , Velocidad del Flujo Sanguíneo/fisiología , Femenino , Vena Femoral/diagnóstico por imagen , Vena Femoral/fisiología , Humanos , Masculino , Embolia Pulmonar/etiología , Flujo Pulsátil/fisiología , Factores de Riesgo , Ultrasonografía , Vena Cava Inferior/fisiología , Insuficiencia Venosa/etiología , Presión Venosa/fisiologíaRESUMEN
Viable pancreas fragments from five human donors were incubated in oxygenated buffered Eagle Medium. The preparation and incubation conditions were based on the method of Scheele and Palade. In Group 1 there was 1-h preincubation with echothiophate (10(-4) M); then, acetylcholine (10(-5) M) was added. After 2 h tissues were prepared for electron microscopy. Acinar injury with vacuole formation was apparent. Many of these changes were observed in fragments incubated only with acetylcholine (10(-5) M) (Group 2) and in incubates with echothiophate only (10(-4) M) (Group 3); only minor changes were seen in controls with Eagle's Medium (Group 4). Large vacuoles were significantly more numerous in Group 1 than in Control Group 4 (p < 0.05). Zymogen granules were depleted in Groups 1, 2, and 3. This depletion was significant in Group 1 when compared with Group 4 (p < 0.02). These results extend previous in vitro results that showed increased amylase release after echothiophate treatment in human pancreas and a left shift in response to acetylcholine.
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Yoduro de Ecotiofato/toxicidad , Pancreatitis/inducido químicamente , Acetilcolina/toxicidad , Enfermedad Aguda , Humanos , Técnicas In Vitro , Microscopía Electrónica , Páncreas/ultraestructura , Pancreatitis/patologíaRESUMEN
OBJECTIVE: To study the effects of local and systemic infusions of calcium on the ultrastructure of the pancreas in cats. DESIGN: Controlled study. INTERVENTIONS: Three groups of four cats each had local infusions (into the splenic artery) of calcium gluconate 0.6 mmol/kg.hour or potassium chloride 1.1 mmol/kg.hour, or sodium chloride 0.9%, for three hours. Two groups of eight cats each had systemic infusions (into the jugular vein) of either calcium gluconate 0.6 mmol/kg.hour or sodium chloride 0.9%, for twelve hours. In the group that was given calcium, the infusion rate was reduced after three hours to 0.3 mmol/kg.hour to maintain the hypercalcaemic state for a further nine hours. RESULTS: Local infusion of calcium caused destruction of acinar cells with hydropic degeneration of nuclei, discharge of cell organelles into the interstitial spaces, and extravasation of red blood cells but no apparent damage to the capillaries. There were no ultrastructural changes of any importance in the groups that received potassium or sodium chloride. Systemic infusion of calcium resulted in a 1.8 fold increase in the ionised calcium concentration in the serum, progressive signs of overstimulation of the Golgi apparatus with hypertrophy, fusion of condensing vacuoles, and disruption of the acinar cell polarization. This was followed by clumping of nuclear chromatin and destruction of acinar cells. CONCLUSION: Acute pancreatitis in cats can result from stimulation and destruction of acinar cells by hypercalcaemia.
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Calcio/efectos adversos , Páncreas/ultraestructura , Pancreatitis/inducido químicamente , Enfermedad Aguda , Animales , Calcio/administración & dosificación , Gatos , Hipercalcemia/inducido químicamente , Hipercalcemia/patología , Infusiones Intraarteriales , Infusiones Intravenosas , Microscopía Electrónica , Páncreas/efectos de los fármacos , Páncreas/patología , Pancreatitis/patologíaRESUMEN
The effect of acute hypercalcemia on pancreatic ultrastructure and the ultrastructural localization of calcium during hypercalcemia were studied in the guinea pig pancreas. After 3 h of i.v. calcium infusion (0.6 mmol/kg/h), hypertrophy and distention of the Golgi apparatus and an increased number of condensing vacuoles were seen. At 6 h, vacuolar fusion and displacement of zymogen granules occurred. At 9 h, irregular distribution of zymogen granules, indentation of the nucleus with chromatin clumping, and inclusion of intact cell organelles were present. Disruption of the plasma membrane and release of cell organelles into the interstitial space were seen. Control animals receiving saline solution (0.9% NaCl) revealed normal pancreatic ultrastructure. The serum ionized calcium values were 0.65 +/- 0.36 mM in controls and 0.71 +/- 0.14, 0.79 +/- 0.21, and 1.22 +/- 0.50 mM at 3, 6, and 9 h of calcium infusion, respectively. The ultrastructural localization of calcium was performed with the pyroantimonate staining technique after 3 h of calcium and saline infusion. Large calcium deposits were found in calcium-treated animals along the plasma membrane and in the Golgi region. The findings indicate that calcium exerts a strong stimulatory effect that eventually leads to the degeneration of the pancreatic acinar cell.
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Hipercalcemia/patología , Páncreas/ultraestructura , Enfermedad Aguda , Animales , Calcio/análisis , Calcio/sangre , Cobayas , Hipercalcemia/sangreRESUMEN
Human pancreas contains two cholinesterase isoenzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In the present study, binding potency of two organophosphates for human cholinesterases were compared by the Ellman method. Echothiophate was found to have much greater potency than iso-OMPA for both cholinesterases. Using Karnovsky histochemical stains on human pancreatic tissue, the same results were confirmed. Dose-response studies with acetylcholine were done on viable pancreas fragments from nine human donors, without pancreatic disease (group I). Cold-preservation time was less than 30 h. Pancreas was minced into fragments, after the technique of Scheele and Palade, placed in Eagle's medium, and gassed with O2. Amylase release was measured by the Phadebas Method and corrected for basal release. There was a dose-dependent response to acetylcholine at 1 and 2 h, with a shift in peak amylase release to the left, when fragments were preincubated in 10(-4) M echothiophate. This indicated a 100-fold increase in sensitivity to acetylcholine. In three patients with chronic pancreatitis (Group II), there were variable patterns of response of amylase release to acetylcholine, and higher basal outputs. In Group III, prolonged storage conditions of over 40 h were tested for 4 pancreas donor tissues. There was no response to acetylcholine. These studies show that for up to 30 h cold storage, fragments of pancreas from human organ donors respond to acetylcholine in dose-dependent manner. An organophosphate, echothiophate (10(-4) M) which inhibits both cholinesterases, increases pancreatic sensitivity to acetylcholine, and these results are similar to findings from canine pancreas fragments, which also showed increased sensitivity.
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Acetilcolina/farmacología , Compuestos Organofosforados/farmacología , Páncreas/efectos de los fármacos , Amilasas/metabolismo , Colinesterasas/metabolismo , Relación Dosis-Respuesta a Droga , Yoduro de Ecotiofato/metabolismo , Yoduro de Ecotiofato/farmacología , Humanos , Compuestos Organofosforados/metabolismo , Páncreas/enzimología , Páncreas/metabolismo , Pancreatitis/inducido químicamente , Tetraisopropilpirofosfamida/metabolismo , Tetraisopropilpirofosfamida/farmacologíaRESUMEN
Hypercalcemia has been associated with acute pancreatitis clinically and in the experimental animal. We studied the pancreatic ultrastructure in acute experimental hypercalcemia. Anesthetized cats (Pentobarbital, 0.55 mg/kg) received Ca++ (Calcium-Gluconate: 0.6 mmol/kgh; n = 4), K+ (KCl: 1.1 mmol/kgh; n = 4) or NaCl (0.9%; n = 4) locally through retrograde infusion into the splenic artery. Biopsies for electron microscopy (EM) were taken at three hours. Eight cats received intravenous Ca++ (0.6 mmol/kgh, 0.3 mmol/kgh after three hours) or NaCl (0.9%) for 12 hours. Biopsies were collected in two animals in three-hour intervals, and in all animals at twelve hours. After local calcium infusion necrotizing pancreatitis was seen macroscopically in the body of the pancreas. Biopsies for EM showed acinar cell necrosis, hydrops of nuclei and mitochondria and needle-like precipitates in the cytoplasma in the center of calcium perfusion. Biopsies taken from the peripheral region of the macroscopically altered tissue revealed desorganisation of the acinar polarisation and the endoplasmic reticulum, with zymogen granules appearing in the basolateral cell-portion. After intravenous calcium administration no macroscopical changes were seen. In EM acinar cells showed dilatation and proliferation of the golgi apparatus and increased number of condensing vacuoles indicating stimulation. Again, disorganisation of acinar cell polarisation was present. Control animals treated with K+ or NaCl showed normal pancreatic ultrastructure. The morphological changes after calcium infusion indicate direct damage to the acinar cell. Our results suggest that hypercalcemia induced pancreatitis could originate in the acinar cell.
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Hipercalcemia/patología , Páncreas/patología , Pancreatitis/patología , Enfermedad Aguda , Animales , Gatos , Microscopía ElectrónicaRESUMEN
Intestinal obstruction remains a major cause of morbidity and mortality in surgical patients. We reviewed the records of 77 patients with mechanical small-bowel obstruction who were treated with endoscopically and fluoroscopically placed Leonard long intestinal tube decompression. Most patients (59%) had failed a trial of nasogastric tube or Miller-Abbott tube decompression. Overall, 29 per cent of patients were able to resolve their obstruction with Leonard tube decompression alone. Subdivision of patients on the basis of the etiology of their obstruction demonstrated a much higher rate of success for tube decompression in adhesive obstruction (37%) versus malignant obstruction (12%) or inflammatory obstruction (no successes). Patients with radiographic and clinical evidence of complete intestinal obstruction were significantly less likely to respond to long intestinal tube treatment (13%). The long intestinal tube was easily passed in all patients. There were no complications of the intubation procedure in our series, and the incidence of tube-related complications was four per cent. We conclude that an initial period of long intestinal tube decompression allows a significant percentage of patients with mechanical small-bowel obstruction to be treated nonoperatively, particularly if a partial obstruction from postoperative adhesions is present. Patients who have failed a trial of nasogastric tube decompression and are poor operative risks should also be considered for long intestinal tube placement.
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Obstrucción Duodenal/terapia , Obstrucción Intestinal/terapia , Intubación Gastrointestinal/métodos , Enfermedades del Yeyuno/terapia , Duodenoscopía , Femenino , Estudios de Seguimiento , Humanos , Intubación Gastrointestinal/efectos adversos , Intubación Gastrointestinal/instrumentación , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The effect of local and systemic calcium administration was tested on the pancreas of cat and guinea pig. After 3 h of local calcium infusion (0.6 mmol/kg x h) via the splenic artery of the cat hemorrhagic pancreatitis could be shown. Control animals treated with potassium (1.1 mmol/kg x h) or 0.9% NaCl alone showed no morphological change in the pancreas. Intravenous administration of calcium (0.6 mmol/kg x h) led to a 1.8-fold increase in serum ionized calcium levels in the cat and a 1.6-fold increase in levels in the guinea pig. The cat showed necrosis of acinar and ductal cells throughout the gland at 12 h. In the guinea pig, acinar cell vacuolisation and cell necrosis started at 3 h, and at 9 h degeneration of entire acini, hydropic swelling and degeneration of ductal cells, and perivascular leukocytic infiltration was present. In both species, a significant increase in the number of intraductal precipitates and a significant increase in urinary amylase output was present in calcium treated animals. The findings suggest that hypercalcemia has a deleterious effect on the pancreas that causes acinar and ductal cell necrosis and eventually pancreatitis.
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Hipercalcemia/complicaciones , Páncreas/patología , Amilasas/sangre , Amilasas/orina , Animales , Calcio/administración & dosificación , Calcio/sangre , Gatos , Cobayas , Hemorragia/etiología , Hemorragia/patología , Hipercalcemia/patología , Infusiones Intraarteriales , Inyecciones Intravenosas , Necrosis , Páncreas/metabolismo , Enfermedades Pancreáticas/etiología , Enfermedades Pancreáticas/patología , Proteínas/metabolismo , Espectrofotometría Atómica , Arteria EsplénicaRESUMEN
Sublethal doses of organophosphate anticholinesterases cause acute pancreatitis in dogs within 2 h. In vitro studies using canine pancreatic fragments have also demonstrated that the peak of amylase release in response to acetylcholine is shifted far to the left after incubation with the organophosphates echothiophate (10(-4) M) or tetraisopropyl pyrophosphoramide (iso-OMPA) (10(-3) M), indicating an increased sensitivity of response. The present in vitro study examined whether there was also an increased susceptibility to acinar cell damage at the electron microscopic level after acetylcholine or cholecystokinin. Minced pieces of whole fresh canine pancreas 2-3 mm in size were placed in buffered Eagle's solution and gassed with 100% O2. After pretreatment 1 h with echothiophate or iso-OMPA, they were then incubated with acetylcholine (10(-5) M). Other tissues preincubated with echothiophate were stimulated with cholecystokinin (10(-9) M). These are submaximal doses for untreated canine pancreatic fragments. After acetylcholine and echothiophate or acetylcholine and iso-OMPA, there was extensive acinar damage with the appearance of large vacuoles and lakes, and interstitial edema. There was evidence of intense supramaximal stimulation and lateral exocytosis. Similar destructive changes were seen after echothiophate and cholecystokinin. In control sections from tissues stimulated with acetylcholine (10(-5) M) or cholecystokinin (10(-9) M, there were lumenal exocytotic patterns typical of submaximal stimulation. Other controls, organophosphate alone and unstimulated basal conditions, showed only minor changes. It is concluded that the increased sensitivity to acetylcholine after organophosphate incubation correlates with an increased susceptibility to acinar ultrastructural damage from acetylcholine and cholecystokinin.
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Acetilcolina/toxicidad , Colecistoquinina/toxicidad , Yoduro de Ecotiofato/toxicidad , Compuestos Organofosforados/toxicidad , Pancreatitis/inducido químicamente , Tetraisopropilpirofosfamida/toxicidad , Acetilcolina/administración & dosificación , Enfermedad Aguda , Animales , Colecistoquinina/administración & dosificación , Perros , Sinergismo Farmacológico , Yoduro de Ecotiofato/administración & dosificación , Microscopía Electrónica , Pancreatitis/patología , Tetraisopropilpirofosfamida/administración & dosificaciónRESUMEN
There are two tissue-fixed cholinesterases in dog pancreas: acetylcholinesterase and butyrylcholinesterase. In the present experiments, an organophosphate that only inhibits butyrylcholinesterase (isopropylpyrophosphoramide, or iso-OMPA) was compared with echothiophate and a nonorganophosphate compound, physostigmine. The latter two agents inhibit both cholinesterases. Fresh canine pancreas from anesthetized dogs was minced into fragments and suspended in Eagle's solution gassed with 100% O2. Amylase release was measured by the Phadebas method. In 2-h dose-response studies, there was a fivefold increase in sensitivity to acetylcholine when fragments were preincubated 1 h with iso-OMPA. There was a 1,000-fold increase in sensitivity when fragments were preincubated for 1 h in echothiophate. Basal amylase release in incubates with echothiophate were also increased. In dose-response studies with CCK-8, iso-OMPA was without effect, but echothiophate treatment resulted in a greater total response to CCK-8. There was a corresponding increase in basal output with echothiophate alone. Physostigmine also potentiates the response to CCK-8. Cumulative responses up to 3 h with half-maximal acetylcholine or half-maximal CCK-8 doses showed enhanced total output in fragments preincubated with echothiophate (p less than 0.05). The enhancement effect was atropine-sensitive to hexamethonium ganglionic blockade. In calcium-free medium, the enhancement with echothiophate was greatly reduced but still present. Inhibitors of both cholinesterases in the pancreas cause a greater total amylase release to sub-maximal doses of acetylcholine and CCK-8 than agents that only inhibit butyrylcholinesterase. Though our data do not provide direct proof, the results could be explained by a greater accumulation of endogenous acetylcholine when both cholinesterases are inhibited.
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Acetilcolinesterasa/metabolismo , Amilasas/metabolismo , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/farmacología , Colinesterasas/metabolismo , Yoduro de Ecotiofato/farmacología , Compuestos Organofosforados/farmacología , Páncreas/enzimología , Fisostigmina/farmacología , Tetraisopropilpirofosfamida/farmacología , Amilasas/antagonistas & inhibidores , Animales , Colecistoquinina/farmacología , Perros , Técnicas In Vitro , Páncreas/efectos de los fármacosRESUMEN
Of 224 consecutive renal transplant patients in a prospective, randomized immunosuppressive trial, candida esophagitis developed in 5 despite nystatin prophylaxis. No differences were noted between cyclosporine and antilymphocyte globulin-azathioprine immunosuppressive treatment. All patients were diabetic, and four were recipients of cadaver kidneys. Candida esophagitis occurred within 6 months after transplantation, and only one patient had recurrence. All patients responded to treatment consisting of 2 to 6 days of intravenous amphotericin B (0.2 to 2 mg/kg total dose). The prevalence of candida esophagitis was not related to rejection episodes. Three of five patients eventually died, one 2 weeks after resolution of candida esophagitis from a hypoglycemic episode, one from acute exacerbation of pulmonary failure and relapsing pancreatitis in association with candida esophagitis and therapy-resistant candidemia, and one 17 months after candida esophagitis from pulmonary edema. Our findings show that candida esophagitis by itself is an easily managed complication, but is also a sign of potentially increased morbidity in these patients.
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Suero Antilinfocítico/uso terapéutico , Azatioprina/uso terapéutico , Candidiasis/epidemiología , Ciclosporinas/uso terapéutico , Esofagitis/epidemiología , Trasplante de Riñón , Adulto , Anfotericina B/uso terapéutico , Candidiasis/tratamiento farmacológico , Ensayos Clínicos como Asunto , Esofagitis/tratamiento farmacológico , Femenino , Humanos , Masculino , Minnesota , Nistatina/uso terapéutico , Estudios Prospectivos , Distribución AleatoriaRESUMEN
This study was undertaken to clarify the issue of whether feedback regulation of pancreatic enzyme secretion occurs in humans. A naturally occurring inhibitor of trypsin and chymotrypsin, the Bowman-Birk inhibitor of soybeans, was used to reduce the activities of these enzymes normally secreted by the pancreas into the duodenum. Pure pancreatic juice was collected by endoscopic retrograde cannulation of the pancreatic duct in a protocol consisting of three periods: period 1 (15 min), collections of juice without return to the duodenum ("washout phase"); period 2 (35 min), intraduodenal infusion of juice to which buffered saline or heat-inactivated Bowman-Birk inhibitor had been added; and period 3 (55 min), intraduodenal infusion of juice in which greater than 90% of the trypsin and chymotrypsin activities had been abolished by treatment with the active inhibitor. Control experiments were included in which untreated juice was infused in period 3 as well as period 2. Enzyme analyses (trypsin, chymotrypsin, elastase, and amylase) of samples of juice collected at 5-min intervals revealed a twofold to threefold increase in the output and concentration of all four enzymes in period 3 compared with period 2. These results thus confirm the existence of feedback control in humans.
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Jugo Pancreático/metabolismo , Inhibidor de la Tripsina de Soja de Bowman-Birk/farmacología , Inhibidores de Tripsina/farmacología , Adulto , Amilasas/metabolismo , Quimotripsina/metabolismo , Femenino , Humanos , Técnicas In Vitro , Masculino , Elastasa Pancreática/metabolismo , Jugo Pancreático/enzimología , Proteínas/metabolismo , Tripsina/metabolismoRESUMEN
We report the occurrence of acute portal vein thrombosis in three patients undergoing endoscopic variceal sclerosis (EVS) for bleeding esophageal varices. All patients received intravenous vasopressin in close proximity to or at the time of EVS. By increasing flow of sclerosant caudally into gastric veins during EVS, vasopressin may predispose to retrograde propagation of thrombus into the portal venous system. Combined use of vasopressin and EVS for treatment of bleeding esophageal varices should be undertaken with caution.