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Biomedical subjects

J Bosch

Publications and source records attributed to J Bosch.

At least 55 records · Page 3Linked to original sources
PubMed2001

Multicenter randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding.

BACKGROUND/AIMS: The dose of somatostatin used for variceal bleeding (250 microg/h) is lower than that proven to effectively decrease portal pressure and azygos blood flow (500 microg/h). Moreover, i.v. somatostatin boluses have greater effects than continuous infusions. The aim of this study was to investigate whether higher doses of somatostatin and repeated boluses may increase its efficacy in controlling variceal bleeding. METHODS: A total of 174 patients with acute variceal bleeding were randomized to receive for 48 h: (A) one 250 microg bolus +250 microg/h infusion; (B) three 250 microg boluses +250 microg/h infusion; (C) three 250 microg boluses +500 microg/h infusion. RESULTS: The three schedules of somatostatin were equally effective in controlling variceal bleeding (73, 75 and 81%, respectively, NS). Multivariate analysis showed active bleeding at endoscopy (n=75) as the only predictor of failure to control bleeding. In these patients, the 500 microg/h infusion dose achieved a higher rate of control of bleeding (82 vs. 60%, P<0.05), less transfusions (3.7 +/- 2.7 vs. 2.5 +/- 2.3 UU, P=0.07) and better survival (93 vs. 70%, P<0.05) than schedules A/B. CONCLUSIONS: Somatostatin is highly effective in controlling variceal bleeding. Patients with active bleeding at emergency endoscopy may benefit from higher doses of somatostatin infusion.

Acute Disease↗
PubMed2001

Assessment of portal hypertension in humans.

Patients suspected of having portal hypertension (either by clinical history, physical examination, or previous diagnosis) should undergo ultrasonography and upper gastrointestinal endoscopy. Ultrasonography, preferably using the duplex technique, can disclose the patency of the portal venous system, the presence of signs of portal hypertension (splenomegaly, portocollateral vessels, repermeabilization of the umbilical vein, and so forth) and provide additional information about liver, biliary, or pancreatic diseases that may be the cause of portal hypertension. Endoscopy can assess the presence and size of gastroesophageal varices, the appearance of the variceal wall, and the presence and severity of portal hypertensive gastropathy. Patients showing a patent portal vein should have hepatic vein catheterization to evaluate the presence of presinusoidal, sinusoidal, or postsinusoidal portal hypertension. Patients in whom presinusoidal portal hypertension is suspected (those having esophageal varices with an HVPG below 10 mm Hg) should have liver biopsy and percutaneous transhepatic measurement of portal pressure. In sinusoidal portal hypertension, the results of endoscopy and HVPG measurement are decisive for the therapeutic management of the patients. The authors' results indicate that, before starting prophylactic therapy with beta-blockers, all patients should undergo at least an hepatic vein catheterization to assess HVPG; it would be preferable to have a variceal pressure measurement also. These measurements must be repeated 3 to 4 weeks after the final dose of therapy has been reached to assess the risk of variceal bleeding or rebleeding.

Blood Pressure Determination↗
PubMed2001

EEG changes during word and figure categorization.

OBJECTIVE: To analyze whether the EEG changes observed during figure and word categorization are compatible with either the dual, the common amodal, or the alternative model (modality-specific codes for words and pictures, where meaning is represented for both in a higher-order amodal system) for semantic knowledge. METHODS: EEG was recorded during word and figure categorization of animals or non-animals in a group of 28 children 8-10 years old. Computation of EEG sources in the frequency domain using variable resolution electrical tomography (VARETA) and their statistical evaluation by statistical parametric mapping were carried out. RESULTS: At all frequencies, there were significant changes between EEG segments prior to the presentation of the stimuli and EEG segments recorded after the stimuli. Post-segments showed more power from 1.56 to 7.02 Hz, and less power than pre-segments from 8 to 12.48 Hz. EEG changes were only observed in the word task at: 3.9 (left occipital), 4.68, 5.46, and 6.24 Hz (temporo-occipital regions). These changes may be associated with visual encoding of words. Frequencies 7.8 and 17.94 Hz increased in prefrontal, anterior cingulate, and anterior temporal regions only during figure categorization. The prefrontal region may be related to object working memory. Thus, these frequencies might be related to figure codification. No significant differences between tasks were observed at 3.12 and 7.02 Hz in very wide brain areas (all lobes except occipital), suggesting that the amodal semantic system storage could be the model compatible with figure and word categorization. CONCLUSIONS: Thus, our results support the modified amodal semantic hypothesis, which advocates that the meanings of both kinds of stimuli are represented in a conceptual memory that receives input from the logogen and iconogen systems.

Cerebral Cortex↗
PubMed2001

Gastric mucosal resistance to acute injury in experimental portal hypertension.

1. The gastric mucosa of portal hypertensive rats exhibits important microvascular changes and a nitric oxide (NO)-dependent hyperemia. This study analyses whether portal hypertensive mucosa exhibits changes in its ability to withstand aggression. 2. Portal hypertension was induced by partial portal vein ligation (PPVL) or common bile duct ligation (CBDL) and gastric damage was induced by oral administration of ethanol or aspirin. Experiments were performed in conscious or anaesthetized rats and some animals were pre-treated with the NO-synthesis inhibitor L-NAME. 3. Conscious PPVL or CBDL rats showed an increased resistance to the damaging effects of ethanol. Oral administration of aspirin produced less gastric damage in PPVL conscious rats than in the control group. 4. The protective effects of portal hypertension were maintained in animals anaesthetized with ketamine and absent when pentobarbital was employed. 5. Pre-treatment with L-NAME restored the damaging effects of ethanol and aspirin in PPVL rats without modifying the level of damage in control animals. 6. Gastric bleeding induced by oral aspirin, as measured by the luminal release of (51)Cr-labelled erythrocytes, was significantly greater in PPVL rats than in control animals. 7. Semi-quantitative analysis by RT--PCR of the mRNA for endothelial NO-synthase (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) levels showed that the expression of iNOS was slightly increased in both the gastric mucosa and smooth muscle of PPVL rats. No changes were observed in eNOS and nNOS expression. 8. Conscious portal hypertensive rats exhibit an enhanced resistance to acute gastric damage which is absent under the influence of some types of anaesthesia and seems related to an increased synthesis of nitric oxide. However, mucosal lesions in these animals show an augmented bleeding per area of injury.

Anesthesia↗
PubMed2001

Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension.

BACKGROUND & AIMS: Octreotide has been suggested for the treatment of variceal bleeding, but detailed dose-finding studies are not available. We performed a dose-finding study investigating the hemodynamic effects of several forms of intravenous octreotide administration. METHODS: Splanchnic hemodynamics and plasma glucagon levels were measured in 68 cirrhotics in baseline conditions and (1) after a double-blind intravenous injection of octreotide (50 microg [n = 9] or 500 microg [n = 8]) or placebo (n = 7); (2) after a 50-microg octreotide bolus followed by continuous infusion of 50 microg/h (n = 8), 250 microg/h (n = 8), or placebo (n = 6); (3) after repeated 50-microg injections of octreotide (n = 9) or placebo (n = 6) after an initial bolus (50 microg octreotide); and (4) after a placebo bolus and continuous octreotide infusion (50 microg/h; n = 7). RESULTS: Placebo caused no significant changes. Octreotide caused a marked and transient decrease in portal pressure and azygos blood flow and an increase in mean arterial pressure. These effects lasted only 5 minutes despite addition of continuous octreotide infusions. Repeated octreotide injections had shorter, less marked effects than the first bolus. A continuous octreotide infusion did not decrease portal pressure. Glucagon levels were markedly reduced by octreotide, but gradually returned to baseline despite continuous infusions or repeated injections of octreotide. CONCLUSIONS: Octreotide injection caused marked but transient reductions in portal pressure and azygos blood flow. Adding a continuous octreotide infusion neither maintained nor prolonged its effects. Repeated boluses caused significant tachyphylaxis. This rapid desensitization to the effects of octreotide may explain the divergent effects achieved with octreotide infusions in acute variceal bleeding.

Adult↗
PubMed2001

Randomized comparison of long-term losartan versus propranolol in lowering portal pressure in cirrhosis.

BACKGROUND & AIMS: It has been suggested that losartan, an angiotensin II (A-II) type 1 receptor blocker, may have a pronounced portal pressure reducing effect, far greater than that of propranolol. This randomized controlled trial compared the hemodynamic and renal effects of continued 6-week administration of losartan (n = 25) vs. propranolol (n = 15) in portal hypertensive patients with cirrhosis treated endoscopically after a variceal bleeding episode. METHODS: Hepatic venous pressure gradient (HVPG), systemic hemodynamics, renal function, and vasoactive factors were measured before and at 6 weeks of treatment. RESULTS: Losartan did not reduce HVPG (-2% +/- 12%, NS) but significantly decreased mean arterial pressure (MAP, -8% +/- 10%, P = 0.001). On the contrary, propranolol significantly reduced HVPG (-10% +/- 11%, P = 0.003) and cardiac output (-16% +/- 12%, P = 0.001) but did not modify MAP (2.5% +/- 10%, NS). Losartan increased A-II levels, reduced aldosterone, and decreased glomerular filtration rate (GFR) in Child B patients. Propranolol did not modify renal function. Adverse events related to therapy were mild and similar in both groups. CONCLUSIONS: Unlike propranolol, long-term losartan administration does not significantly reduce HVPG in patients with cirrhosis treated after a variceal bleeding episode, and it caused hypotension and reduced GFR in patients with moderate liver failure. Therefore, losartan is not an alternative to propranolol in preventing variceal rebleeding.

Adult↗
PubMed2001

Effects of blood volume restitution following a portal hypertensive-related bleeding in anesthetized cirrhotic rats.

The aim of this study was to investigate the influence of different strategies of blood volume restitution in the outcome of portal hypertension-related bleeding in anesthetized cirrhotic rats. Gastrointestinal hemorrhage was induced by sectioning a first order branch of the ileocolic vein in 38 cirrhotic rats (common bile duct ligation and occlusion). The subsequent hypovolemic shock was treated with no transfusion (n = 17), moderate transfusion (50% of expected blood loss, 5 mL, n = 11), and total transfusion (100% of expected blood loss, 10 mL, n = 10). At the end of the blood transfusion period (minute 15), mean arterial pressure (MAP) partially recovered in rats receiving moderate transfusion or no transfusion but decreased in the 10-mL transfusion group ( downward arrow 12 +/- 43%, P < .05 vs. no transfusion and 5 mL transfusion). After transfusion, groups given no or 5 mL transfusion remained hemodynamically stable. However, rats receiving 10 mL transfusion continued to deteriorate with persistent bleeding and progressive fall in MAP ( downward arrow 65 +/- 12%; P < .05 vs. no transfusion and 5 mL transfusion). Collected blood loss was significantly greater in the 10-mL group (20.0 +/- 1.5 g) than in groups given 5 mL (15.9 +/- 2.8 g; P < .05) or no transfusion (13.2 +/- 2.1 g; P < .05 vs. 10 mL and 5 mL transfusion). Survival in the no transfusion group was 47%. Rats given 5-mL transfusion had 64% survival. The worst survival was observed in the 10-mL transfusion group (0% survival; P < .05). We concluded that a transfusion policy aimed at completely replacing blood loss worsens the magnitude of bleeding and mortality from portal hypertensive-related bleeding in cirrhotic rats. On the contrary, moderate blood transfusion allowed hemodynamic stabilization and increased survival.

Animals↗
PubMed2001

Renal failure after upper gastrointestinal bleeding in cirrhosis: incidence, clinical course, predictive factors, and short-term prognosis.

To assess the incidence, clinical course, predictive factors, and prognosis of renal failure in patients with cirrhosis and gastrointestinal bleeding, 175 consecutive episodes of gastrointestinal bleeding in 161 patients were analyzed. Renal failure occurred in 20 (11%) episodes and was transient in 8 episodes and nontransient in 12. Renal failure was more common in patients with cirrhosis than in a control population of bleeding patients without cirrhosis matched by age and severity of the bleeding episode. Among 39 clinical and laboratory variables obtained at admission or during hospitalization related with the bleeding episode or with liver and renal function, the presence of hypovolemic shock, number of packed red blood cells transfused, Child-Pugh class at admission, and baseline platelet count were independent predictors of renal failure. The development of renal failure and hypovolemic shock was the only independent predictors of in-hospital mortality. Mortality rate among the 20 episodes with renal failure was 55% (11 deaths) as compared with only 3% (5 deaths) in the 155 episodes without renal failure (P <.01). The development of nontransient renal failure entailed a much greater mortality as compared with transient renal failure (10 of 12 [83%] vs. 1 of 8 [12%]; P <.01). In conclusion, renal failure is a common event in patients with cirrhosis and gastrointestinal bleeding, the occurrence of which is mainly related to the severity of bleeding and baseline liver function. Renal failure is a strong predictor of mortality in patients with cirrhosis and gastrointestinal bleeding.

Adolescent↗
PubMed2001

Propranolol for the prevention of first esophageal variceal hemorrhage: a lifetime commitment?

Although beta blockers have had significant impact in the treatment of portal hypertension, the question of how long they should be continued for prevention of variceal hemorrhage remains unknown. Prospective studies on beta blockers to prevent variceal hemorrhage lack long-term follow-up, and indefinite administration of beta blockers for primary prevention of variceal bleeding has become standard practice. The aim of this study was to determine the outcomes of patients in whom beta blocker therapy was discontinued. Patients completing a prospective, randomized, double-blind, placebo-controlled trial of propranolol for the primary prevention of variceal hemorrhage were tapered off of propranolol and placebo and followed prospectively for subsequent events. Of the 49 patients in the follow-up study (25 former propranolol, 24 former placebo), 9 experienced variceal hemorrhage (6 former propranolol, 3 former placebo). Following withdrawal of propranolol, the freedom from variceal bleeding was not significantly different between these 2 groups of patients, suggesting that the protective effect of propranolol against variceal hemorrhage, noted previously, was no longer present. Seventeen patients died (12 former propranolol, 5 former placebo) during the follow-up study. Cumulative survival was longer in the placebo group. These trends for EVH and survival were opposite to those observed in the original study population while patients were taking medication. When propranolol is withdrawn, the risk of variceal hemorrhage returns to what would be expected in an untreated population. Patients who discontinue beta blockers experience increased mortality compared with an untreated population. These observations support the current practice of indefinite prophylactic therapy.

Adrenergic beta-Antagonists↗
PubMed2001

Stenosis of the suprahepatic inferior vena cava as a complication of transjugular intrahepatic portosystemic shunt in Budd-Chiari patients.

We report 2 patients with Budd-Chiari (BC) syndrome secondary to thrombogenic conditions who underwent transjugular intrahepatic portosystemic shunt (TIPS) placement because of refractory ascites and impending liver failure. After TIPS placement, there was marked symptomatic relief and improvement in liver function, but the courses of both patients were complicated by the development of an inferior vena cava (IVC) syndrome caused by segmental stenosis of the suprahepatic IVC just at the outflow jet of the TIPS at 11 and 9 months later. One patient underwent liver transplantation, and the other patient, caval angioplasty and stenting. Stenosis of the IVC represents an unrecognized complication of TIPS in patients with BC syndrome.

Adult↗
PubMed2001

Neutrophil adhesion is impaired in the mesentery but not in the liver sinusoids of portal hypertensive rats.

Altered leukocyte/cytokine response to inflammation has been observed in human and experimental portal hypertension. The aim of this study was to characterize leukocyte adhesion in portal hypertensive (PPVL) rats stimulated with endotoxin. Leukocyte rolling, adhesion, and migration assessed by intravital microscopy were impaired in mesenteric venules after lipopolysaccharide administration (150 microg/kg) in PPVL vs. sham-operated rats. Analysis of leukocyte L-selectin expression and soluble L-selectin showed that this defective adhesion was related to increased L-selectin shedding. In vitro experiments using isolated leukocytes treated with phorbol 12-myristate 13-acetate showed that monocytes and neutrophils but not lymphocytes were hyperreactive to cell activation, as measured by CD11b overexpression and increased L-selectin shedding in PPVL rats. However, neutrophil emigration in liver sinusoids and in the lung 3 h after endotoxin injection were similar in both groups of animals. Thus the alterations in leukocyte activation and adhesion molecule expression observed in this study may contribute to a better understanding of the higher susceptibility and severity of bacterial infections in cirrhotic patients with portal hypertension.

Animals↗
PubMed2001

Isosorbide mononitrate in the prevention of first variceal bleed in patients who cannot receive beta-blockers.

BACKGROUND & AIMS: Nonselective beta-blockers (beta-blockers) are very effective in preventing first variceal bleeding (FVB) in patients with cirrhosis. However, 15%-25% of patients have contraindications or develop severe side effects precluding its use. The present study evaluates whether isosorbide-5-mononitrate (Is-MN) effectively prevents variceal bleeding in patients with contraindications or who could not tolerate beta-blockers. METHODS: One hundred thirty-three consecutive cirrhotic patients with gastro-esophageal varices and contraindications or intolerance to beta-blockers were included in a multicenter, prospective, double-blind randomized controlled trial. Sixty-seven were randomized to receive Is-MN, and 66 to receive placebo. RESULTS: There were no significant differences in the 1- and 2-year actuarial probability of experiencing a FVB between the 2 treatment groups. Presence of variceal red signs at endoscopy was the only variable independently associated with an increased risk of variceal bleeding on follow-up (relative risk 3.4; P < 0.01). Survival and adverse events were similar in the 2 groups. There were no significant differences in the incidence of ascites or changes in renal function. CONCLUSIONS: Is-MN does not reduce the incidence of FVB in patients with cirrhosis and esophageal varices who cannot be treated with beta-blockers because contraindications or intolerance to these drugs, suggesting that Is-MN has no place in the primary prophylaxis of variceal bleeding.

Adrenergic beta-Antagonists↗
PubMed2001

Pharmacological treatment of portal hypertension.

In liver cirrhosis, increased resistance to portal blood flow is the primary factor in the pathophysiology of portal hypertension. The recognition of a dynamic component in hepatic resistance due to the active-reversible contraction of different elements of the portohepatic bed, has led to the active development of hepatic vasodilators. On the other hand, a significant increase in portal blood flow caused by arteriolar splanchnic vasodilation and hyperkinetic circulation, aggravates portal hypertension and provides the rational for the use of splanchnic vasoconstrictors, such as beta-blockers, vasopressin derivatives and somatostatin and its analogs. This review covers current developments in the treatment of portal hypertension.

Animals↗
PubMed2000

Oxidative diphosphonylation of 1,4-dihydropyridines and pyridinium salts

An oxidative double phosphonylation of dihydropyridines 1 and pyridinium salts 2 is achieved through the use of dialkyl phosphites, DDQ, and triethylamine. Acceptable to good yields of 2, 6-diphosphonylated-1,2-dihydropyridines 3 are obtained in a one-pot reaction involving tandem nucleophilic addition/oxidation processes. Isomerization of 3 to the more stable 2,4-diphosphonylated-1, 4-dihydropyridine 4 was observed in some cases.

Journal Article↗
PubMed2000

Synthesis of enantiopure trans-3,4-disubstituted piperidines. An enantiodivergent synthesis of (+)- and (-)-paroxetine.

Reaction of (R)-phenylglycinol with methyl 5-oxopentanoate gave either bicyclic lactam cis-1 (the kinetic product) or its isomer trans-1 (under equilibrating conditions) as the major products, which were converted to the corresponding (cis or trans) unsaturated lactams 4 and 5. On treatment with lithium alkyl (or aryl) cyanocuprates, these chiral building blocks undergo conjugate addition to give enantiopure trans-3,4-substituted 2-piperidone derivatives in high yield and stereoselectivity. The synthetic potential of this transformation is illustrated by the synthesis of (+)-femoxetine and the two enantiomers of the known antidepressant paroxetine.

Antidepressive Agents, Second-Generation↗