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Biomedical subjects

J Bosch

Publications and source records attributed to J Bosch.

At least 163 records · Page 9Linked to original sources
PubMed1996

Increased blood hemoglobin attenuates splanchnic vasodilation in portal-hypertensive rats by nitric oxide inactivation.

BACKGROUND & AIMS: Nitric oxide, which is quenched by hemoglobin, has been implicated in the pathogenesis of portal hypertension. The aim of this study was to investigate the effects of increasing blood hemoglobin concentration by erythropoietin treatment on the gastrointestinal vasodilation associated with portal hypertension. METHODS: Portal-hypertensive and sham-operated rats treated with erythropoietin were studied 2 weeks after surgery. Hemodynamic and rheological parameters were measured in baseline conditions and after N(G)-nitro-L-arginine methyl ester (L-NAME) or sodium nitroprusside treatment. RESULTS: In portal-hypertensive rats, erythropoietin attenuated the increase in gastric mucosal and superior mesenteric artery blood flows and the decrease in arterial blood pressure and splanchnic vascular resistances. Those parameters were not affected by erythropoietin in sham-operated rats. A direct vascular effect of erythropoietin was ruled out by the lack of changes in blood pressure or mesenteric blood flow after intravenous erythropoietin administration and by a similar in vitro relaxation to acetylcholine in mesenteric artery rings. In portal-hypertensive rats, erythropoietin blunted the blood pressure response to sodium nitroprusside and attenuated the gastric and mesenteric blood flow response to L-NAME. CONCLUSIONS: Gastrointestinal vasodilation associated with portal hypertension can be attenuated by increasing blood hemoglobin concentration. Inactivation of overproduced NO by hemoglobin may account for this effect.

Animals↗
PubMed1996

Acute and chronic cyclooxygenase blockage in portal-hypertensive rats: influence in nitric oxide biosynthesis.

BACKGROUND & AIMS: Prostacyclin and nitric oxide have been involved in the hyperkinetic syndrome in portal hypertension. The aim of this study was to investigate the relative contribution and possible interaction between prostacyclin and NO in this circulatory abnormality. METHODS: Portal vein-ligated and sham-operated rats received indomethacin and vehicle either on a short-term (5 mg/kg subcutaneously) or long-term basis (5 mk.kg-1.day-1, continuous 7-day infusion with an osmotic minipump). Measurements of arterial pressure and superior mesenteric arterial flow (mL.min-1.kg-1, ultrasonic flow probe) were then performed before and after NG-nitro-L-arginine methyl ester (L-NAME) injection (13 mg/kg intravenously). RESULTS: Short-term or long-term indomethacin treatment had no effect in sham-operated rats but significantly decreased mesenteric arterial flow in portal-hypertensive rats. Mesenteric flow remained higher after long-term than after short-term indomethacin treatment (54.5 +/- 2 vs. 46.1 +/- 2; P = 0.01). This blunted response to long-term indomethacin treatment was associated with an enhanced response to L-NAME, shown by greater increments in arterial pressure (29% +/- 3%) and mesenteric arterial resistance (209 +/- 22%) in indomethacin-treated rats than in rats receiving vehicle (19% +/- 2% and 130% +/- 20%; P < 0.05). CONCLUSIONS: Both prostacyclin and NO contributed to splanchnic hyperemia in portal-hypertensive rats. There was an enhanced release of NO after long-term prostacyclin inhibition, suggesting that both vasodilatory systems interact, promoting splanchnic hyperemia in portal hypertension.

Animals↗
PubMed1996

Nitric oxide-mediated beta 2-adrenoceptor relaxation is impaired in mesenteric veins from portal-hypertensive rats.

BACKGROUND & AIMS: beta-Adrenergic relaxation seems to be mediated by nitric oxide. The aim of this study was to evaluate changes induced by portal hypertension in beta 2-adrenergic vasorelaxation. METHODS: Isolated rat mesenteric veins were relaxed by salbutamol, and nerve-mediated vasocontractions were induced by electrical field stimulation. Responses were evaluated in the presence of NG-nitro-L-arginine methyl ester (L-NAME) or tetrodotoxin. Immunocytochemical techniques were used for localization of neuronal NO synthase. RESULTS: Salbutamol-induced relaxations were decreased in rings from portal-hypertensive animals. L-NAME reduced these relaxations, but its effects were more pronounced in sham-operated rats. Tetrodotoxin decreased the effect of salbutamol only in rings from sham-operated animals. Combination of L-NAME and tetrodotoxin did not exert a greater effect than either of these agents alone. Veins from portal-hypertensive animals were more sensitive to S-nitroso-N-acetyl penicillamine. L-NAME increased vasocontractions by electrical stimulation only in rings from sham-operated rats. Veins from portal-hypertensive animals exhibited a specific degeneration of NO-containing nerve endings. CONCLUSIONS: beta 2-Adrenergic relaxation is impaired in mesenteric veins from portal-hypertensive rats, possibly as a result of a defective neuronal release of NO.

Adrenergic beta-Agonists↗
PubMed1996

Double-blind randomized controlled trial comparing terlipressin and somatostatin for acute variceal hemorrhage. Variceal Bleeding Study Group.

BACKGROUND & AIMS: Terlipressin and somatostatin decrease portal pressure and have been used to treat variceal hemorrhage, but they have not been adequately compared. The aim of this study was to compare the efficacy and safety of these drugs in the treatment of variceal bleeding in cirrhotic patients. METHODS: Of 161 patients with variceal bleeding. 80 were randomized to receive (double-blind) intravenous terlipressin (2 mg/4 h) and 81 to receive somatostatin (continuous infusion of 250 micrograms/h after an intravenous injection of 250 micrograms). Success of therapy was defined as a 24-hour bleeding-free period within 48 hours from randomization. RESULTS: Success of therapy was similar with terlipressin (80%) and somatostatin (84%). In patients with Child's class A and B disease, terlipressin was effective in 52 of 60 (87%) and somatostatin in 48 of 55 (87%). Success rates in class C were 60% and 77% (P = 0.33). No differences were observed in rebleeding rates (30% vs. 28.4%) and 6-week mortality rates (13 vs. 13 patients). Incidence of side effects was significantly higher in the terlipressin group (38.8% vs. 23.5%; P = 0.042). Severe side effects requiring intervention occurred in 5 of 80 and 4 of 81 patients, respectively. CONCLUSIONS: Terlipressin and somatostatin are highly effective as first-line treatment of variceal hemorrhage in cirrhotic patients. The low incidence of severe side effects suggests that drug therapy may be maintained for longer periods to prevent early rebleeding.

Acute Disease↗
PubMed1996

Physical exercise increases portal pressure in patients with cirrhosis and portal hypertension.

BACKGROUND & AIMS: In healthy subjects, exercise promotes marked hemodynamic and humoral changes characterized by an increase in cardiac output, a redistribution of blood flow to muscular territories under activity, and an increase in sympathoadrenergic activity. The aim of this study was to investigate the extent to which hemodynamic and humoral changes caused by exercise may influence portal and systemic hemodynamics in patients with cirrhosis. METHODS: In 8 patients with liver cirrhosis and portal hypertension, arterial pressure, cardiac output, portal pressure (as hepatic venous pressure gradient [HVPG]), and hepatic blood flow were measured before and at two steps of cycling exercise equivalent to 30% and 50% of their peak workload. RESULTS: Exercise (at 30% of peak work-load) significantly increased arterial pressure and cardiac output and decreased systemic vascular resistance. This was associated with a significant increase in HVPG (from 16.7 +/- 1.5 to 19.2 +/- 1.6 mm Hg; P < 0.01) and a significant reduction in hepatic blood flow (from 1291 +/- 216 to 1034 +/- 152 mL-min-1; P < 0.05). All of these changes were intensified at 50% of target workload. CONCLUSIONS: The present study shows that moderate exercise increases portal pressure and may therefore increase the risk of variceal bleeding in patients with esophageal varices. These findings suggest that cirrhotic patients with portal hypertension should be advised of potential risks during exercise.

Exercise↗
PubMed1996

Existence of a platelet-adhesion defect in patients with cirrhosis independent of hematocrit: studies under flow conditions.

A defect in hemostasis has been repeatedly reported in patients with cirrhosis. However, the nature of this defect has not been fully characterized. We explored adhesive and cohesive functions of platelets from cirrhotic patients at different stages of disease development. The response of platelets to standard activating agents was tested by aggregometric procedures. The interaction of platelets with subendothelial components was explored in a perfusion system in which blood was exposed (shear rate, 800/s; 10 minutes) to denuded segments of rabbit aorta. Platelet interactions in these perfusions were analyzed morphometrically. Results were always compared with those obtained in similar studies using blood obtained from healthy subjects. Aggregation studies showed abnormal responses for single or several agonists. Abnormalities in aggregation were more evident in patients with severe disease (Child-Pugh class C), although they occasionally were abnormal for single agonists (ADP or U46619) in patients with less severe disease (Child-Pugh classes A or B). All the patient classes showed impaired platelet-subendothelial interactions (P < .01 vs. healthy subjects) that were not justified by the relative thrombocytopenia present in the more severely affected patients. Experimental increases in hematocrit in patients at stages B and C did not improve platelet-subendothelial interactions. Platelets from cirrhotic patients interact defectively with subendothelial components under flow conditions. The adhesion defect is more evident and consistent than the aggregation defects and may already be present in patients with mild liver failure. This adhesion defect may contribute to the defective hemostasis observed in cirrhotic patients.

Adult↗
PubMed1996

Rationale and design of a large study to evaluate the renal and cardiovascular effects of an ACE inhibitor and vitamin E in high-risk patients with diabetes. The MICRO-HOPE Study. Microalbuminuria, cardiovascular, and renal outcomes. Heart Outcomes Prevention Evaluation.

OBJECTIVE: To describe the rationale and design of a large international study (microalbuminuria, cardiovascular, and renal outcomes [MICRO] in the HOPE [Heart Outcomes Prevention Evaluation] study) of an ACE inhibitor and vitamin E for the prevention of diabetic nephropathy (DN) and cardiovascular disease (CVD) in patients with diabetes and microalbuminuria (MA). RESEARCH DESIGN AND METHODS: A total of 3,657 diabetic subjects, including 1,129 with MA, are randomly allocated to receive the ACE inhibitor ramipril (or placebo) and vitamin E (or placebo) for 4 years in a two-by-two factorial design. Diabetic subjects are a subset of the 9,541 subjects enrolled in the HOPE study. RESULTS: The development of DN in microalbuminuric diabetic subjects and the development of MA in normoalbuminuric subjects, as well as cardiovascular death, myocardial infarction, and storke, are the main outcomes. The correlation of changes in albuminuria with changes in carotid atherosclerosis documented in a subset of subjects will also be analyzed. CONCLUSIONS: The effect of both an ACE inhibitor and vitamin E on the progression of renal and CVD in patients with diabetes is being assessed in the MICRO-HOPE study.

Albuminuria↗
PubMed1995

Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis.

In patients with variceal bleeding as a complication of hepatic cirrhosis, propranolol therapy reduces the risk of recurrent variceal haemorrhage. However, the relation between portal pressure response to pharmacological treatment and clinical events has not been well defined. This relation was prospectively investigated in 69 cirrhotic patients receiving continued propranolol therapy after an episode of variceal bleeding. Hepatic venous pressure gradient (HVPG) was measured before and at 3 months of continued drug therapy. At 3 months HVPG had fallen by 20% or more in 25 patients. During follow-up of 28 (SD 17) months rebleeding occurred in 2 of these 25 patients compared with 23 of 44 who had lesser reductions in HVPG. Cumulative probability of rebleeding at 1, 2, and 3 years was 4%, 9%, and 9% in patients with a decrease in HVPG > or = 20%, and 28%, 39%, and 66% in patients with a decrease in HVPG < 20% (p < 0.001, log-rank test). On multivariate analysis, a decrease in HVPG > or = 20% was the only independent predictor of rebleeding (relative risk 0.09, 95% CI 0.02-0.41. Of the 8 patients in whom the HVPG fell to 12 mm Hg or less, none rebled. This study suggests that measurement of the HVPG response to pharmacotherapy will provide useful prognostic information on the long-term risk of variceal rebleeding.

Administration, Oral↗
PubMed1995

Laparoscopic cholecystectomy in cirrhotic patients. Indication or contradiction?

Liver cirrhosis is considered a contraindication to laparoscopic cholecystectomy for the moment. Here we are reporting on results in the surgical treatment of gallstone disease in cirrhotic patients by laparoscopic means. We reviewed the experience over the final period of time in 11 patients since the introduction of laparoscopic procedures in our unit. The index of conversion rate was 9.1% (1/11). The morbidity was nil. The average length of hospital stay was 1.8 days (1-6 days). We propose the use of laparoscopic cholecystectomy in gallstone disease in patients with liver cirrhosis as first-line surgical treatment.

Adult↗
PubMed1995

Frequency source analysis in patients with brain lesions.

In a previous study (Harmony et al. 1993) we observed that the volume of lesions was correlated only with delta power, while the volume and density of edema showed a significant correlation with theta and alpha power, suggesting two independent origins of activity in the delta and theta bands in patients with space-occupying lesions. Our goal in this paper is to show, through a different technique, in a narrow band spectral analysis, that brain lesions are characterized by activity in the delta domain and that edema is better correlated with activity within the theta range. Frequency source analysis based on the Maximum Likelihood (ML) test for rejection of isotropicity was applied to the EEG at rest of 36 patients with space-occupying intracranial lesions. The ML test was rejected at frequencies below 1 Hz and in the low range of the delta rhythm in 31 patients. The origin of the equivalent dipoles at these frequencies was within the volume of the lesion in 27 patients. In 15 patients out of 19 with vasogenic edema the ML test was rejected at frequencies in the theta range. The equivalent dipoles at these frequencies were all within the volume of the edema.

Astrocytoma↗
PubMed1995

Continuous prazosin administration in cirrhotic patients: effects on portal hemodynamics and on liver and renal function.

BACKGROUND & AIMS: Hepatic vascular resistance is influenced by alpha-adrenergic tone. The aim of this study was to investigate the effects of continuous blockade of alpha-adrenoceptors with prazosin on hemodynamics, liver function, and renal function and whether the association of propranolol or furosemide enhances the portal pressure lowering effect of prazosin. METHODS: Cirrhotic patients with portal hypertension were studied at baseline and after a 3-month course of prazosin (n = 18) or placebo (n = 10). RESULTS: No changes were observed in the placebo group. Prazosin decreased the hepatic venous pressure gradient (HVPG) while increasing hepatic blood flow. Liver function improved as shown by an increase in hepatic and intrinsic hepatic clearances of indocyanine green and galactose elimination capacity. A significant reduction in mean arterial pressure and systemic vascular resistance was associated with increases in plasma renin activity and aldosterone concentration and a decrease in glomerular filtration rate. The plasma volume increased significantly, and 6 patients developed edema. The association of propranolol (n = 8) but not furosemide (n = 7) to prazosin increased the reduction in HVPG and attenuated the increase in plasma renin activity. CONCLUSIONS: In cirrhotic patients, continuous prazosin administration reduces portal pressure and improves liver perfusion and function but favors sodium and water retention. The association of propranolol enhances the decrease in portal pressure, suggesting a potential benefit from this combined therapy.

Adrenergic alpha-Antagonists↗
PubMed1995

Evidence against a role for inducible nitric oxide synthase in the hyperdynamic circulation of portal-hypertensive rats.

BACKGROUND/AIMS: Excessive nitric oxide biosynthesis caused by expression of inducible NO synthase has been implicated in the hyperdynamic circulation of portal hypertension. The aim of the study was to investigate whether inducible NO synthase is expressed in portal hypertension an accounts for the hyperdynamic circulation. METHODS: In study 1, NO synthase activities were measured by the conversion of L-arginine to citrulline in tissues from portal-hypertensive, cirrhotic, and sham-operated rats and from normal rats pretreated with endotoxin and after long-term administration of dexamethasone, which inhibits the expression of inducible NO synthase. In study 2, systemic and splanchnic hemodynamics (radiolabeled microspheres) and gastric blood flow (hydrogen gas clearance and reflectance spectrophotometry) were measured in portal-hypertensive rats after long-term administration of dexamethasone (0.25 mg.kg-1.day-1) or vehicle. RESULTS: In study 1, constitutive and inducible NO synthase activities in portal-hypertensive or cirrhotic rats were similar to those observed in sham-operated rats. The significant increase in the inducible activity observed after endotoxin injection was prevented when rats received long-term treatment with dexamethasone. In study 2, cardiac index, portal-pressure, portal venous inflow, and gastric blood flow were similar in dexamethasone-or vehicle-treated portal-hypertensive rats. CONCLUSIONS: These results to not support a role for an increased expression of the inducible NO synthase in the hyperdynamic circulation of portal hypertension.

Amino Acid Oxidoreductases↗
PubMed1995

Bone remodelling in human immunodeficiency virus-1-infected patients. A histomorphometric study.

The aim of this study was to identify and describe possible alterations of bone histomorphometry in patients with human immunodeficiency virus (HIV-1) infection and to assess the relation between these alterations and disease severity. Forty-four HIV-1-infected patients seen successively at our hospital were evaluated for the study. In an attempt to avoid confounding factors as far as possible, we excluded patients who fulfilled any of the following criteria: age less than 18 or greater than 40 years; recent history of extended bed rest; previous diagnosis of metabolic bone disease, renal insufficiency, or hepatic failure; clinical or echographic signs of liver cirrhosis; diabetes mellitus or previous diagnosis of other endocrine diseases; drug therapy that could act on bone metabolism; and/or moderate to severe nutritional alteration. Twenty-two patients (13 men, 9 women; age: 27.9 +/- 4.1 years, mean +/- standard deviation) were included in the study. Plasma and urine biochemistry and calcium-regulating hormones were determined. Bone mineral content was measured on vertebrae L2 to L4 and on the neck and intertrochanteric areas of the femur by dual-photon absorptiometry. A transiliac bone biopsy was performed after double-tetracycline labelling, with histomorphometric study of undecalcified bone. Serum osteocalcin was found to be lower in patients who, according to the Centers for Disease Control (CDC) classification, had greater disease severity, and showed a positive correlation with the number of CD4+ T lymphocytes. No alterations in bone densitometry were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Anemia increases gastric blood flow in noncirrhotic and cirrhotic patients.

BACKGROUND: Previous studies in rats have demonstrated that anemia induces a significant increment in gastric mucosal blood flow. In the present study, we investigated whether chronic anemia induces similar changes in gastric blood perfusion in humans, and if this effect is also present in cirrhotic patients in whom gastric blood flow is usually increased in basal conditions. METHODS: Gastric mucosal blood perfusion was assessed by means of laser-Doppler flowmetry and reflectance spectrophotometry applied through the endoscope. RESULTS: Anemia significantly increases laser-Doppler signal in cirrhotic (2.3 +/- 0.11 vs 2.9 +/- 0.22 volts, p < 0.05) and noncirrhotic patients (1.71 +/- 0.15 vs 2.24 +/- 0.17, p < 0.05). In anemic patients the index of hemoglobin concentration of the gastric mucosa, assessed by reflectance spectrophotometry, was significantly decreased in cirrhotic patients (107.6 +/- 4.7 vs 95.5 +/- 3.3, p < 0.05) and noncirrhotic patients (93.9 +/- 4.1 vs 76.1 +/- 4.2, p < 0.01), whereas the index of oxygen saturation was increased (36.7 +/- 0.7 vs 40.4 +/- 1.4, p = 0.05; and 36.4 +/- 1.1 vs 43.2 +/- 1.9, p < 0.01, respectively). CONCLUSIONS: In conclusion, chronic anemia is associated with an enhanced gastric blood perfusion reflected by an increased laser-doppler signal and gastric mucosal oxygen index despite a decrease in gastric hemoglobin concentration. In cirrhotic patients, anemia promotes a further increment in its basal gastric hyperemia.

Anemia↗