Update of the PANCCO clinical practice guidelines for the treatment of ulcerative colitis in the adult population.

Ulcerative colitis (US) is a chronic disease of unknown etiology. It is incurable and its clinical course is intermittent, characterized by periods of remission and relapse. The prevalence and incidence of the disease has been increasing worldwide. The update presented herein includes the participation of healthcare professionals, decision-makers, and a representative of the patients, all of whom declared their conflicts of interest. Answerable clinical questions were formulated, and the outcomes were graded. The information search was conducted on the Medline/PubMed, Embase, Epistemonikos, and LILACS databases, and covered grey literature sources, as well. The search was updated on November 30, 2020, with no restrictions regarding date or language. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification system was implemented to establish the strength of the recommendation and quality of evidence. A formal consensus was developed, based on the RAND/UCLA methodology and the document was peer reviewed. The short version of the Clinical Practice Guidelines for the Treatment of Ulcerative Colitis in the Adult Population is presented herein, together with the supporting evidence and respective recommendations. In mild-to-moderate UC, budesonide MMX is an option when treatment with 5-ASA fails, and before using systemic steroids. In moderate-to-severe UC, infliximab, adalimumab, vedolizumab, ustekinumab, and tofacitinib can be used as first-line therapy. If there is anti-TNF therapy failure, ustekinumab and tofacitinib provide the best results. In patients with antibiotic-refractory pouchitis, anti-TNFs are the treatment of choice.

Sclerosing encapsulating peritonitis: imaging findings in an uncommon entity. / Peritonitis esclerosante encapsulante: hallazgos en imágenes de una entidad poco frecuente.

OBJECTIVES: To describe the most characteristic imaging findings for sclerosing encapsulating peritonitis, with an emphasis on the computed tomography findings. CONCLUSION: The incidence of sclerosing encapsulating peritonitis is low. The pathophysiology of this condition is unclear. Two types are recognized: idiopathic and secondary; the secondary type is generally a complication of peritoneal dialysis. Its nonspecific clinical presentation and the absence of blood markers mean that sclerosing encapsulating peritonitis is usually diagnosed late. Thus, it is important to know the imaging signs; these include thickening and calcification of the peritoneum and dilation of bowel loops with thickening and calcification of bowel walls, whether in isolation or in association with loculated ascites. Although ultrasonography allows the complexity of the collections to be evaluated, computed tomography is the most useful technique for the general assessment of the signs mentioned above.

Special situations in inflammatory bowel disease: First Latin American consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) (Second part). / Situaciones especiales en la enfermedad inflamatoria intestinal: primer consenso latinoamericano de la Pan American Crohn's and Colitis Organisation (PANCCO) (Segunda parte).

This is the first Latin American Consensus of the Pan American Crohn's and Colitis Organisation (PANCCO) regarding special situations in patients with inflammatory bowel disease (IBD). The aim of this consensus is to raise awareness in the medical community in all Latin American countries with respect to pregnancy, vaccinations, infections, neoplasms, including colorectal cancer, and pediatric issues in patients with IBD.

Total nutritional therapy: a nutrition education program for physicians.

OBJECTIVE: Almost half of all hospitalized patients are malnourished with low physician awareness or implementation of nutrition support. To address this problem, a 2-day immersion course in clinical nutrition for physicians was developed by the Latin American Federation of Parenteral and Enteral Nutrition (FELANPE) with support from Abbott Laboratories. The goal of Total Nutritional Therapy (TNT) is to help physicians utilize this nutrition knowledge to increase their awareness of malnutrition and implementation of nutritional therapy. Since 1997, over 8,000 physicians have completed the TNT course in 16 Latin American countries. RESEARCH METHODS & PROCEDURES: During 1999 and 2000, 675 participants responded to a survey 6 months after having completed the TNT course to determine what impact the course had on the use of nutrition assessment, nutrition support teams, or nutrition consultations in their clinical practice, and if they had participated in any nutrition association or conferences. RESULTS: The majority of physicians who completed the survey increased their use of nutrition assessment and time dedicated to nutrition therapy, and increased the number of their patients placed on nutrition therapy. CONCLUSIONS: The TNT course has been shown to be an efficient model of clinical nutrition education for general physicians. The course should be considered as part of the training of medical residents.

Seroprevalencia de Helicobacter pylori en hemodializados / xxx

AIM: (a) to establish Hp infection seroprevalence among patients under chronic dialysis and to compare it with that of general population, (b) to assess the relationship between Hp prevalence and parameters associated with a higher morbidity, such as serum albumin levels, dialysis adequacy, and quality of life in this population. METHODS: Ninety-three consecutive patients of both genders (58 M/35 F), X 57.5 +/- 17.2 years old, with end-stage chronic renal failure on maintenance dialysis were included. All of them received dialysis at Hospital Italiano, Buenos Aires. The presence of anti-Hp antibodies was established and its prevalence was compared with a control group. In all cases, serum albumin levels and time in dialysis were determined. In addition, dialysis adequacy was established by KT/V and quality of life was measured with Karnofskys index. Patients and controls were matched according variables associated with Hp infection in our country, i.e., age, socioeconomic and education levels. RESULTS: Ninety-three dialysis patients were matched with 93 controls. According to the quick serological test, 44 out of 93 (47.3%) dialyzed patients and 55 out of 93 (53.6%) controls were Hp positive (ns). Forty-one out of 76 patients (53.9%) with a serum albumin level 3.5 g/dl and 3/17 (17.6%) with a serum albumin level < 3.5 g/dl were anti-Hp positive (odds ratio, 0.06; 95% CI, 0.01-0.39; p < 0.01). Fifty-five out of 80 patients (69.2%) with Kt/V > 1.2 and 6/13 (43.8%) with Kt/V 1.2 Pounds were anti-Hp positive (odds ratio, 0.10; 95% CI, 0.02-0.65; p < 0.05). Four out of 15 patients (26.7%) with Karnofskys index > 70, and 40/78 (51.3%) with Karnofskys index < or = 70 were anti-Hp positive (odds ratio, 0.37; 95% CI, 0.06-2.95, p = 0.26). CONCLUSION: According to our results, dialysis patients do no represent a high-risk group of Hp infection. Those individuals with higher morbidity and mortality rates as evidenced by low serum albumin levels or by a low Kt/V have a lower Hp prevalence, perhaps due to a poor immune response o due to the use of antibiotics. Therefore, Hp infection screening en dialysis units does not differ from the guidelines developed in Maastrich for the general population. (AU)

Seroprevalencia de Helicobacter pylori en hemodializados

AIM: (a) to establish Hp infection seroprevalence among patients under chronic dialysis and to compare it with that of general population, (b) to assess the relationship between Hp prevalence and parameters associated with a higher morbidity, such as serum albumin levels, dialysis adequacy, and quality of life in this population. METHODS: Ninety-three consecutive patients of both genders (58 M/35 F), X 57.5 +/- 17.2 years old, with end-stage chronic renal failure on maintenance dialysis were included. All of them received dialysis at Hospital Italiano, Buenos Aires. The presence of anti-Hp antibodies was established and its prevalence was compared with a control group. In all cases, serum albumin levels and time in dialysis were determined. In addition, dialysis adequacy was established by KT/V and quality of life was measured with Karnofsky's index. Patients and controls were matched according variables associated with Hp infection in our country, i.e., age, socioeconomic and education levels. RESULTS: Ninety-three dialysis patients were matched with 93 controls. According to the quick serological test, 44 out of 93 (47.3%) dialyzed patients and 55 out of 93 (53.6%) controls were Hp positive (ns). Forty-one out of 76 patients (53.9%) with a serum albumin level 3.5 g/dl and 3/17 (17.6%) with a serum albumin level < 3.5 g/dl were anti-Hp positive (odds ratio, 0.06; 95% CI, 0.01-0.39; p < 0.01). Fifty-five out of 80 patients (69.2%) with Kt/V > 1.2 and 6/13 (43.8%) with Kt/V 1.2 Pounds were anti-Hp positive (odds ratio, 0.10; 95% CI, 0.02-0.65; p < 0.05). Four out of 15 patients (26.7%) with Karnofsky's index > 70, and 40/78 (51.3%) with Karnofsky's index < or = 70 were anti-Hp positive (odds ratio, 0.37; 95% CI, 0.06-2.95, p = 0.26). CONCLUSION: According to our results, dialysis patients do no represent a high-risk group of Hp infection. Those individuals with higher morbidity and mortality rates as evidenced by low serum albumin levels or by a low Kt/V have a lower Hp prevalence, perhaps due to a poor immune response o due to the use of antibiotics. Therefore, Hp infection screening en dialysis units does not differ from the guidelines developed in Maastrich for the general population.

[Helicobacter pylori seroprevalence in dialysis patients]. / Seroprevalencia de Helicobacter pylori en hemodializados.

AIM: (a) to establish Hp infection seroprevalence among patients under chronic dialysis and to compare it with that of general population, (b) to assess the relationship between Hp prevalence and parameters associated with a higher morbidity, such as serum albumin levels, dialysis adequacy, and quality of life in this population. METHODS: Ninety-three consecutive patients of both genders (58 M/35 F), X 57.5 +/- 17.2 years old, with end-stage chronic renal failure on maintenance dialysis were included. All of them received dialysis at Hospital Italiano, Buenos Aires. The presence of anti-Hp antibodies was established and its prevalence was compared with a control group. In all cases, serum albumin levels and time in dialysis were determined. In addition, dialysis adequacy was established by KT/V and quality of life was measured with Karnofsky's index. Patients and controls were matched according variables associated with Hp infection in our country, i.e., age, socioeconomic and education levels. RESULTS: Ninety-three dialysis patients were matched with 93 controls. According to the quick serological test, 44 out of 93 (47.3%) dialyzed patients and 55 out of 93 (53.6%) controls were Hp positive (ns). Forty-one out of 76 patients (53.9%) with a serum albumin level 3.5 g/dl and 3/17 (17.6%) with a serum albumin level < 3.5 g/dl were anti-Hp positive (odds ratio, 0.06; 95% CI, 0.01-0.39; p < 0.01). Fifty-five out of 80 patients (69.2%) with Kt/V > 1.2 and 6/13 (43.8%) with Kt/V 1.2 Pounds were anti-Hp positive (odds ratio, 0.10; 95% CI, 0.02-0.65; p < 0.05). Four out of 15 patients (26.7%) with Karnofsky's index > 70, and 40/78 (51.3%) with Karnofsky's index < or = 70 were anti-Hp positive (odds ratio, 0.37; 95% CI, 0.06-2.95, p = 0.26). CONCLUSION: According to our results, dialysis patients do no represent a high-risk group of Hp infection. Those individuals with higher morbidity and mortality rates as evidenced by low serum albumin levels or by a low Kt/V have a lower Hp prevalence, perhaps due to a poor immune response o due to the use of antibiotics. Therefore, Hp infection screening en dialysis units does not differ from the guidelines developed in Maastrich for the general population.

Seroprevalencia de Helicobacter pylori en hemodializados. / [Helicobacter pylori seroprevalence in dialysis patients]

AIM: (a) to establish Hp infection seroprevalence among patients under chronic dialysis and to compare it with that of general population, (b) to assess the relationship between Hp prevalence and parameters associated with a higher morbidity, such as serum albumin levels, dialysis adequacy, and quality of life in this population. METHODS: Ninety-three consecutive patients of both genders (58 M/35 F), X 57.5 +/- 17.2 years old, with end-stage chronic renal failure on maintenance dialysis were included. All of them received dialysis at Hospital Italiano, Buenos Aires. The presence of anti-Hp antibodies was established and its prevalence was compared with a control group. In all cases, serum albumin levels and time in dialysis were determined. In addition, dialysis adequacy was established by KT/V and quality of life was measured with Karnofskys index. Patients and controls were matched according variables associated with Hp infection in our country, i.e., age, socioeconomic and education levels. RESULTS: Ninety-three dialysis patients were matched with 93 controls. According to the quick serological test, 44 out of 93 (47.3

) dialyzed patients and 55 out of 93 (53.6

) controls were Hp positive (ns). Forty-one out of 76 patients (53.9

) with a serum albumin level 3.5 g/dl and 3/17 (17.6

) with a serum albumin level < 3.5 g/dl were anti-Hp positive (odds ratio, 0.06; 95

CI, 0.01-0.39; p < 0.01). Fifty-five out of 80 patients (69.2

) with Kt/V > 1.2 and 6/13 (43.8

) with Kt/V 1.2 Pounds were anti-Hp positive (odds ratio, 0.10; 95

CI, 0.02-0.65; p < 0.05). Four out of 15 patients (26.7

) with Karnofskys index > 70, and 40/78 (51.3

) with Karnofskys index < or = 70 were anti-Hp positive (odds ratio, 0.37; 95

CI, 0.06-2.95, p = 0.26). CONCLUSION: According to our results, dialysis patients do no represent a high-risk group of Hp infection. Those individuals with higher morbidity and mortality rates as evidenced by low serum albumin levels or by a low Kt/V have a lower Hp prevalence, perhaps due to a poor immune response o due to the use of antibiotics. Therefore, Hp infection screening en dialysis units does not differ from the guidelines developed in Maastrich for the general population.

Colonic proteinases: increased activity in patients with ulcerative colitis.

In order to study the colonic intraluminal proteinase-antiproteinase imbalance under inflammatory conditions, we determined proteolytic activity (PA), alpha-1-antitrypsin and the activities of trypsin, chymotrypsin and neutrophil elastase in feces from patients with ulcerative colitis (UC) comparing the results with a control group. A fecal sample was obtained from each 25 patients with ulcerative colitis and 10 control subjects were studied. The severity of the disease was assessed by the Truelove index. Proteolytic activity was measured using azocasein as proteolytic substrate. The fecal concentration of alpha-1-antitrypsin was measured by radial immunodiffusion and the activities of the enzymes were measured using specific substrates. We found an increase in fecal PA, alpha-1-antitrypsin and neutrophil elastase in patients with UC and the correlation between the severity of the disease and the PA was statistically significant (r = 0.62, P < 0.05). We conclude that elevated colonic proteinase activity could contribute to the pathophysiology of ulcerative colitis.

Stimulation of inflammatory mediators secretion by chemotactic peptides in rat colitis model.

Colonic inflammation was produced in rats by chemotactic peptides acting on polymorphonuclear leucocytes. Instillation during one hour of formylated tripeptide: formylmethionyl-leucyl-phenylalanine (FMLP) and a tetrapeptide: alanine-glycine-sefine-glutamine (AGSG) into rat colon caused erosions and exulcerations. Neutrophils increased secondary to instillation, predominantly with FMLP, and mucus depletion was marked in the cecum. Chloride ion secretion and mucosal permeability were significatively greater in the colonic lumen with the chemotactic peptides. Histamine and serotonin concentration were greater in the colonic fluid in animals treated with the peptides. These observations could suggest that the presence of chemotactic peptides at the colonic lumen produce changes at the mucosal wall, that would participate in generation and perpetuation of the colonic inflammation.

Stimulation of inflammatory mediators secretion by chemotactic peptides in rat colitis model

Colonic inflammation was produced in rats by chemotactic peptides acting on polymorphonuclear leucocytes. Instillation during one hour of formylated tripeptide: formylmethionyl-leucy-phenylalanine (FMLP) and a tetrapeptide: alanine-glycine-sefine-glutamine (AGSG) into rat colon caused erosions and exulcerations. Neutrophils increased secondary to instillation, predominantly with FMLP, and mucus depletion was marked in the cecum. Chloride ion secretion and mucosal permeability were significatively greater in the colonic lumen with the chemotactic peptides. Histamine and serotonin concentration were greater in the colonic fluid in animals treated with the peptides. These observations could suggest that the presence of chemotactic peptides at the colonic lumen produce changes at the mucosal wall, that would participate in generation and perpetuation of the colonic inflammation.

Stimulation of inflammatory mediators secretion by chemotactic peptides in rat colitis model

Colonic inflammation was produced in rats by chemotactic peptides acting on polymorphonuclear leucocytes. Instillation during one hour of formylated tripeptide: formylmethionyl-leucy-phenylalanine (FMLP) and a tetrapeptide: alanine-glycine-sefine-glutamine (AGSG) into rat colon caused erosions and exulcerations. Neutrophils increased secondary to instillation, predominantly with FMLP, and mucus depletion was marked in the cecum. Chloride ion secretion and mucosal permeability were significatively greater in the colonic lumen with the chemotactic peptides. Histamine and serotonin concentration were greater in the colonic fluid in animals treated with the peptides. These observations could suggest that the presence of chemotactic peptides at the colonic lumen produce changes at the mucosal wall, that would participate in generation and perpetuation of the colonic inflammation. (AU)

Fecal lactate and short bowel syndrome.

In patients with short bowel syndrome (SBS), the carbohydrate overload to the colon may disturb the normal pattern of colonic fermentation with production of D-lactic acid and subsequent development of a metabolic D-lactic acidosis. We measured D-lactic acid in blood, urine, and feces, as well as the composition of fecal water and fecal reducing substances from 11 patients with SBS, comparing the results with those from normal subjects. The fecal water from patients with SBS was characterized by low pH, potassium, and volatile fatty acids, high osmotic gap, and high concentration of L- and D-lactic acid. Five of 11 had abnormal amounts of fecal reducing substances. Fecal D-lactic acid was increased in nine of 11 patients. However, none of these patients showed D-lactic acid in urine, and only one had a very low concentration in plasma. These results show that D-lactic acid was overproduced in the colon of most of the patients with SBS. However, other factors such as absorption or impaired D-lactic acid metabolism may be necessary for a plasmatic increase of D-lactic acid.

Colonic proteolysis following pancreatic duct ligation in the rat.

Luminal proteolytic activity (PA) of different colonic segments was ascertained in animals subjected to pancreatic duct ligation (PDL) and in control rats. The PDL rats revealed a significant PA reduction in the cecum, proximal colon (P < 0.01), and distal colon (P < 0.005). Proteolytic activity, trypsin, and chymotrypsin activity in control rats diminished progressively from the cecum to the distal colon. Conversely in PDL rats, we found maximal PA in distal colon. The conclusion is drawn that a significant proportion of colonic proteolytic activity can be attributed to pancreatic proteases with a maximal contribution at cecum level.

[Role of nitric oxide in alterations of the systemic and splanchnic hemodynamics in a experimental model of portal hypertension]. / Papel del óxido nítrico en las alteraciones de la hemodinámica sistémica y esplácnica en un modelo experimental de hipertensión portal.

Recent experimental studies have suggested that an increase in the synthesis of nitric oxide, a powerful vasodilator secreted by endothelial cells, plays a role in the hemodynamic disturbances associated to portal hypertension. The present study was addressed to investigate the effects of L-NNA (a specific inhibitor of nitric oxide) on systemic and splanchnic hemodynamics in portal hypertensive rats, induced by partial portal vein ligation. Intravenous infusion of L-NNA (50 ug/kg/min) significantly increased systemic blood pressure and decreased cardiac output as measured by radiolabeled microspheres. A significant increase in systemic and splanchnic vascular resistance was also observed in L-NNA-treated rats; whereas portal blood flow decreased significantly, L-NNA did not modify portal pressure. Pretreatment with L-arginine (300 mg/Kg, i.v.) prevented the hemodynamic changes induced by L-NNA. Similar values of endotoxin levels were detected in both groups of animals. In the control group, L-NNA caused a mild but significant increase of mean arterial pressure; no significant changes on the other hemodynamic parameters were observed. These results suggest that an increase in endogenous synthesis of nitric oxide may play an important role in hemodynamic disturbances associated with chronic portal hypertension.

[Do the physical characteristics of radiopaque markers modify the results of the measurement of colonic transit time?]. / Los caracteres físicos de los Marcadores Radiopacos modifican los resultados de la medición del tiempo de tránsito colónico?

UNLABELLED: This study was performed in 15 healthy control subjects (8 males- age 23-70 and 7 females age 20-74) as a way to compare the total and segmental colonic transit time with two different type of radiopaque markers. One type of markers was 3 mm cut sections of a radiopaque polietilene 14 French Levine tube, with a medium weight of 64.3 mg and a specific gravity (SG) of 1.28. The other type were 7 mm lenticular insoluble barium (lentils) with medium weight of 231 mg and a SG of 1.87. Each subject ingested 20 markers of each type with the breakfast and front and profile plain films of the abdomen were taken 24 and 48 hs after. The total colonic transit time for the polietilene markers was 17.7 hs and 27.3 hs for the barium type (BM) (p < 0.001). The segmental transit time for right colon was 2.4 hs (PM) and 9.7 hs (PM) and 9.7 hs (BM) (p < 0.001) in the left colon 9.5 hs (PM) and 11.3 hs (BM) and in rectoanun 5.9 hs (BM) with no statistical significance. CONCLUSION: the physical characteristics of the radiopaque markers can modify the results of the colonic transit times.

Los caracteres fisicos de los marcadores radiopacos modifican los resultados de la medicion del tiempo de transito colonico? / The physical characteristics of radiopaque markers modify the results of the measurement of colonic transit time?

El objetivo de este trabajo es comparar en sujetos controles sanos el tiempo de tránsito colónico total y segmentario con dos tipos de marcadores radiopacos utilizados en nuestro medio. Se estudiaron 16 personas sanas, 8 varones de 23 a 70 años de edad y 7 mujeres de 20 a 74 años con dieta habitual. Un tipo de marcadores corresponde a cilindros huecos de 3 mm de longitud onbtenidos de sondas de Levine 14 French con un peso medio de 64.3 mg y una gravedad específica (GE) de 1.28, el otro tipo de marcadores corresponde a grageas lenticulares indisolubles de bario, de 7 mm de diámetro, 231 mg de peso y GE específica de 1.87. Cada individuo ingirió luego del desayuno 20 marcadores de cada tipo y se obtuvieron radiografías simples de abdomen en decúbito dorsal y lateral izquierdo de pelvis a las 24 hs y 48 hs. El tiempo de tránsito colónico total para marcadores de polietileno fue de 17.7 hs. y para los de bario 27.3 hs. (p < 0.001). En el colon derecho fue respectivamente de 2,4 y 9,7 hs. (p < 0.001) en el izquierdo de 9,5 y 11,3 y en el recto ano de 5,9 y 6,3 (sin significancia estadística). Concluimos que los caracteres físicos de los marcadores radioopacos modifican los resultados del tiempo de tránsito colónico

Los caracteres físicos de los Marcadores Radiopacos modifican los resultados de la medición del tiempo de tránsito colónico? / [Do the physical characteristics of radiopaque markers modify the results of the measurement of colonic transit time?]

This study was performed in 15 healthy control subjects (8 males- age 23-70 and 7 females age 20-74) as a way to compare the total and segmental colonic transit time with two different type of radiopaque markers. One type of markers was 3 mm cut sections of a radiopaque polietilene 14 French Levine tube, with a medium weight of 64.3 mg and a specific gravity (SG) of 1.28. The other type were 7 mm lenticular insoluble barium (lentils) with medium weight of 231 mg and a SG of 1.87. Each subject ingested 20 markers of each type with the breakfast and front and profile plain films of the abdomen were taken 24 and 48 hs after. The total colonic transit time for the polietilene markers was 17.7 hs and 27.3 hs for the barium type (BM) (p < 0.001). The segmental transit time for right colon was 2.4 hs (PM) and 9.7 hs (PM) and 9.7 hs (BM) (p < 0.001) in the left colon 9.5 hs (PM) and 11.3 hs (BM) and in rectoanun 5.9 hs (BM) with no statistical significance. Conclusion: the physical characteristics of the radiopaque markers can modify the results of the colonic transit times.

Papel del óxido nítrico en las alteraciones de la hemodinámica sistémica y esplácnica en un modelo experimental de hipertensión portal. / [Role of nitric oxide in alterations of the systemic and splanchnic hemodynamics in a experimental model of portal hypertension]

Recent experimental studies have suggested that an increase in the synthesis of nitric oxide, a powerful vasodilator secreted by endothelial cells, plays a role in the hemodynamic disturbances associated to portal hypertension. The present study was addressed to investigate the effects of L-NNA (a specific inhibitor of nitric oxide) on systemic and splanchnic hemodynamics in portal hypertensive rats, induced by partial portal vein ligation. Intravenous infusion of L-NNA (50 ug/kg/min) significantly increased systemic blood pressure and decreased cardiac output as measured by radiolabeled microspheres. A significant increase in systemic and splanchnic vascular resistance was also observed in L-NNA-treated rats; whereas portal blood flow decreased significantly, L-NNA did not modify portal pressure. Pretreatment with L-arginine (300 mg/Kg, i.v.) prevented the hemodynamic changes induced by L-NNA. Similar values of endotoxin levels were detected in both groups of animals. In the control group, L-NNA caused a mild but significant increase of mean arterial pressure; no significant changes on the other hemodynamic parameters were observed. These results suggest that an increase in endogenous synthesis of nitric oxide may play an important role in hemodynamic disturbances associated with chronic portal hypertension.