MRI pallidal hyperintensity and brain atrophy in cirrhotic patients: two different MRI patterns of clinical deterioration?

In cirrhotic patients, even in a stable nonencephalopathic state, MRI may show cerebral atrophy and increased signal in globus pallidus on T1-weighted sequences. We investigated the relationship between cerebral atrophy and increased pallidal signal and the clinical status of 30 cirrhotic patients. We found a weak association between the two MRI findings. There were different patterns of clinical variables related to the imaging findings. Performance on motor tasks involving speed correlated with the pallidal signal and plasma ammonia levels but not with atrophy. Test results for memory and frontal-premotor function were associated with brain atrophy but not with the pallidal signal or with ammonia.

Persistence of MRI hyperintensity of the globus pallidus in cirrhotic patients: a 2-year follow-up study.

We investigated the long-term persistence and short-term stability of globus pallidus (GP) hyperintensity on T1-weighted MRI in 19 cirrhotic patients. After a mean interval of 25.8 months, the hyperintensity of the GP persisted in 17 patients. Hyperintensity disappeared in two patients with hepatocarcinoma, indicating that hyperintensity can revert to normal in circumstances other than liver transplants. Ten patients participated in a 6-month study with repeated evaluations of GP signal intensity, plasma ammonia levels, and selected neuropsychological tests. The GP signal was fairly stable during the follow-up, and the variables considered maintained significant relationships. GP hyperintensity appears as a stable indicator of the functional status of cirrhotic patients.

Neurospectroscopic alterations and globus pallidus hyperintensity as related magnetic resonance markers of reversible hepatic encephalopathy.

In patients with chronic hepatic encephalopathy, proton magnetic resonance spectroscopy can be used to detect specific metabolic abnormalities in the brain; MRI shows a hyperintense globus pallidus on T1-weighted sequences. We investigated the relationship between these two MR findings in a series of 25 patients with the use of quantitative data and a multiple regression analysis model. The cerebral increase in glutamine compounds and the decrease in myoinositol and choline correlated separately with globus pallidus hyperintensity, and each was complementary in accounting for this imaging finding. Such as association suggests that spectroscopic and imaging alterations are two different expressions of the reversible events that occur in the brain of patients with hepatic encephalopathy in that both disappear after liver transplantation. Globus pallidus hyperintensity seems to be a global indicator of the cerebral metabolic disorder, and the spectroscopic pattern denotes the specific metabolic alterations.

Sucralfate and cimetidine as maintenance treatment in the prevention of duodenal ulcer recurrence.

This multicenter trial investigated the ability of the cytoprotective agent sucralfate and the antisecretory agent cimetidine to prevent ulcer relapses. Seventy-one patients with recently healed duodenal ulcer were included, randomly assigned to one of the two treatment groups, and administered sucralfate 2 g per day or cimetidine 400 mg per day for six months; the treatment period was followed by another six months of follow-up without treatment. The response to therapy was evaluated by systematic single-blind endoscopy controls during the sixth and the 12th months. Quantitative (42 percent relapse rate with sucralfate and 52 percent with cimetidine) as well as qualitative (20 percent silent relapses with sucralfate and 47 percent with cimetidine) differences were observed, although these could not be demonstrated to be statistically significant.

Relationship between cerebral perfusion in frontal-limbic-basal ganglia circuits and neuropsychologic impairment in patients with subclinical hepatic encephalopathy.

UNLABELLED: Early detection of neuropsychologic impairment in cirrhotic patients with subclinical hepatic encephalopathy (SHE) is important for their prognosis and quality of life. Abnormal MRI and MR spectroscopy (MRS) findings have been proposed as early markers of brain damage in these patients, but the role of functional neuroimaging in this field still has to be defined. In this study, the SPECT perfusion pattern in patients with SHE was investigated, and the relationship between regional cerebral blood flow (rCBF) and the MRI, MRS, neuropsychologic evaluation and biochemical data of these patients was assessed. METHODS: Data were obtained from 13 cirrhotic patients with SHE and 13 age-matched healthy volunteers. Fasting venous blood ammonia and manganese sampling and a battery of standardized neuropsychologic tests related to basal ganglia function and sensitive to the effects of liver disease were all performed on the same day. MRI and 99mTc-hexamethyl propyleneamine oxime SPECT were performed within 2 wk. RESULTS: A pattern of decreased prefrontal rCBF was found in patients with SHE compared with healthy volunteers. Basal ganglia and mesial temporal rCBF correlated inversely with performance on motor tasks involving speed (Purdue pegboard test) and frontal premotor function (Luria graphic alternances and Stroop tests). Thalamic rCBF correlated positively with T1-weighted MRI signal hyperintensity in the globus pallidus and with abnormal MRS findings. Neither the MRI signal intensity of the globus pallidus nor MRS correlated with neuropsychologic test results. CONCLUSION: Cirrhotic patients with SHE show a SPECT pattern of impaired prefrontal perfusion that does not seem to account for their neuropsychologic deficits. On the other hand, perfusion in some parts of the limbic system and limbic-connected brain regions, such as the striatum and the mesial temporal regions, increased with neuropsychologic impairment. These findings suggest that brain SPECT may be more sensitive than MRI in delineating cirrhotic patients requiring in-depth clinical testing to reveal basal ganglia-related neuropsychologic alterations.

A practical guide to the management of bleeding ulcers.

In patients with acute haemorrhage from peptic ulcers, emergency endoscopy should be performed as soon as safely possible after resuscitation to detect the bleeding lesion, to define stigmata of recent haemorrhage, and to perform endoscopic therapy when required. Subsequent management will be determined by the results of diagnostic endoscopy. Ulcers with a clean base or with flat blood spots will not require endoscopic therapy: the patient can be discharged early after resuscitation and the institution of treatment to promote ulcer healing. Ulcers in which endoscopy discloses active arterial bleeding or a nonbleeding visible vessel should be treated, as these signs denote a high risk of an unfavourable outcome, and the efficacy of endoscopic therapy has been demonstrated when these signs are identified. In keeping with the available data, antisecretory therapy, vasoconstrictor drugs and tranexamic acid cannot be recommended as treatment for an acute ulcer bleeding episode. On the other hand, it has been shown in controlled trials that endoscopic therapy significantly reduces the incidence of further bleeding and the requirement for emergency surgery in patients with ulcers with active arterial bleeding or a nonbleeding visible vessel. Meta-analyses of these studies have also shown a significant decrease in mortality with endoscopic therapy. Among the available endoscopic methods for haemostasis, injection therapy is a valid choice since its efficacy has been similar to that of thermal methods in comparative studies, while its simplicity, tolerability and low cost are great advantages. A second endoscopic treatment can be attempted in patients with further haemorrhage after the initial endoscopic therapy, and permanent haemostasis can be achieved in half of these cases. However, the decision to perform this second endoscopic treatment should be taken individually, as the routine use of such a procedure could increase mortality by delaying surgery.

[Portasystemic shunt in the treatment of gastropathy caused by portal hypertension]. / Derivación portosistémica en el tratamiento de la gastropatía por hipertensión portal.

Gastropathy by portal hypertension constitutes the second cause of digestive hemorrhage in these patients following esophagogastric varices. Beta-blocker drugs seem efficient in treatment as occasionally does therapeutic endoscopy. The case of a patient with chronic liver disease with upper digestive hemorrhage is presented. The patient did not respond to medical treatment with beta-blockers nor to endoscopy (thermic and sclerosant). Portocaval anastomosis was performed with no posterior hemorrhagic relapse. The use of shunt surgery has been suggested in this pathology given the rarity of its presentation in patients with this type of operation. The satisfactory evolution of the patient seems to confirm this hypothesis.

[The prognostic signs of digestive hemorrhage due to peptic ulcer]. / Signos pronósticos en la hemorragia digestiva por ulcus péptico.

UNLABELLED: A series of clinical and endoscopic signs have been described, which have predictive value in the evolution and mortality of peptic ulcer hemorrhage. Accepted clinical parameters of severity are: age above 60, associated severe disease, hypovolemic shock at admission. Endoscopic prognostic signs for persistence or recurrence of hemorrhage are: active bleeding, either spurting or oozing, a visible vessel. Other endoscopic signs such as the presence of a dark clot, black dots, red spots over the ulcer, do not have prognostic value. IN CONCLUSION: The presence of active bleeding or a visible vessel in a patient with peptic ulcer bleeding, especially when aged more than 60 and with associated severe disease is indicative of recurrence or persistence of the hemorrhage and of greater mortality. In this group of patients therapeutic endoscopy is mandatory.

[Nadolol as an adjuvant to sclerotherapy of esophageal varices for prevention of recurrent hemorrhaging]. / Nadolol como coadyuvante a la escleroterapia de varices esofágicas en la profilaxis de recidiva hemorrágica.

AIM: to assess whether nadolol could improve the results of sclerotherapy in the prevention of varices rebleeding. EXPERIMENTAL DESIGN: prospective study in which patients with cirrhosis and Child-Pugh's class A or B and with their first hemorrhage from esophageal varices, diagnosed by emergency endoscopy, were included. After initial control of bleeding with emergency sclerotherapy, the patients were randomized into two groups to receive long-term variceal sclerotherapy either alone (group 1) or plus nadolol (group 2). Sclerotherapy was performed by intravariceal injection of 5% ethanolamine at days 0, 4 10, 30 and then monthly until eradication of varices. Nadolol was administered during the whole follow-up in a dose to reduce resting pulse rate by 25% (mean final dose: 82 +/- 31 mg/d). PATIENTS: During a two year period (1989-1991), 40 patients with cirrhosis (from alcohol abuse in 48%), were included. 18 patients were allocated in group 1 and 22 in group 2. RESULTS: Both groups were well-matched for clinical, biological and endoscopic data. Follow-up was similar in both (24.3 +/- 10.6 months in group 1 vs 27.3 +/- 9.8 in group 2). Nine patients in group 1 (50%) and 13 in group 2 (59%) rebled during the follow-up, with a total number of 14 and 22 rebleeding episodes respectively (p = NS). There were no differences between the two groups when considering rebleeding index, transfusional requirements per rebleeding episode and the cumulative percentage of patients free from rebleeding. Severe complications attributable to treatment were observed in 22% of patients in group 1 and in 27% in group 2 (p = NS). Two patients died in each group. CONCLUSIONS: In patients undergoing long-term sclerotherapy for prevention of variceal rebleeding, nadolol confers no additional benefit.

[Value of ultrasonography in the early diagnosis of hepatocellular carcinoma]. / Valor de la ecografía en el diagnóstico precoz del carcinoma hepatocelular.

The size and the treatment of 135 hepatocellular carcinomas (HCC) has been analyzed, comparing patients diagnosed by a US screening program (group 1) and these diagnosed outside this program (group 2) to determine whether US screening on patients with chronic liver disease is able to diagnose (HCC) at an early stage. alpha-fetoprotein levels above 500 U/ml were considered as diagnostic. Twenty (46.5%) out of 43 patients from group 1 showed a HCC < 5 cm. vs. 14/92 (15.2%) in group 2 (p = 0.001). Only 5.9% of the HCC < 5 cm. showed AFP > 500 U/ml. vs. 29.7% of the advanced HCC (p = 0.003). 88.3% of patients of group 1 vs. 63% of group 2 received specific treatment for HCC (p = 0.002). By means of US screening it is possible to diagnose HCC of smaller size and more susceptible to treatment. AFP is not useful in the early diagnosis of HCC.

[An analysis of hospital bacterial infections in cirrhotic patients undergoing selective intestinal decontamination]. / Análisis de las infecciones bacterianas intrahospitalarias en pacientes cirróticos sometidos a descontaminación intestinal selectiva.

Cirrhotic patients with ascites and low levels of ascitic fluid C3 and total protein and cirrhotic patients with gastrointestinal hemorrhage are at high risk of infection. Selective intestinal decontamination with oral norfloxacin is useful to decrease the incidence of infections in cirrhotic patients at high risk. This study analyzes hospital acquired bacterial infections in cirrhotic patients with ascites and low levels of total protein in ascitic fluid (n = 53) and cirrhotic patients with gastrointestinal hemorrhage (n = 26), both submitted to selective intestinal decontamination with norfloxacin during the hospitalization. Seven patients developed eight infections (8.8%): three patients with ascites and low levels of total protein in ascitic fluid and four patients with gastrointestinal hemorrhage (5.6% vs 15.3%, pNS). Gram negative bacilli were not isolated in any case, but Gram positive cocci were isolated in seven cases. These results suggest that Gram positive cocci must be empirically covered when infection is suspected in cirrhotic patients submitted to selective intestinal decontamination. The analysis of antibiograms in these infections showed a high sensitivity of Gram positive cocci to amoxycillin and clavulanic acid, which could be used as empirical treatment when infection is suspected in these patients.

[Digestive hemorrhage due to duodenal angiodysplasia in the periampullary area]. / Hemorragia digestiva por angiodisplasia duodenal en región periampular.

A case of digestive hemorrhage due to duodenal angiodysplasia at the level of the Vater papilla is presented. Diagnosis was achieved by analysis of the surgical resection sample.

Clinical trial: a randomized controlled study on prevention of variceal rebleeding comparing nadolol + ligation vs. hepatic venous pressure gradient-guided pharmacological therapy.

BACKGROUND: Hepatic venous pressure gradient (HVPG) monitoring of therapy to prevent variceal rebleeding provides strong prognostic information. Treatment of nonresponders to beta-blockers +/- nitrates has not been clarified. AIM: To assess the value of HVPG-guided therapy using nadolol + prazosin in nonresponders to nadolol + isosorbide-5-mononitrate (ISMN) compared with a control group treated with nadolol + ligation. METHODS: Cirrhotic patients with variceal bleeding were randomized to HVPG-guided therapy (n = 30) or nadolol + ligation (n = 29). A Baseline haemodynamic study was performed and repeated within 1 month. In the guided-therapy group, nonresponders to nadolol + ISMN received nadolol and carefully titrated prazosin and had a third haemodynamic study. RESULTS: Nadolol + prazosin decreased HVPG in nonresponders to nadolol + ISMN (P < 0.001). Finally, 74% of patients were responders in the guided-therapy group vs. 32% in the nadolol + ligation group (P < 0.01). The probability of rebleeding was lower in responders than in nonresponders in the guided therapy group (P < 0.01), but not in the nadolol + ligation group (P = 0.41). In all, 57% of nonresponders rebled in the guided-therapy group and 20% in the nadolol + ligation group (P = 0.05). The incidence of complications was similar. CONCLUSIONS: In patients treated to prevent variceal rebleeding, the association of nadolol and prazosin effectively rescued nonresponders to nadolol and ISMN, improving the haemodynamic response observed in controls receiving nadolol and endoscopic variceal ligation. Our results also suggest that ligation may rescue nonresponders.

Clinical trial: intravenous pantoprazole vs. ranitidine for the prevention of peptic ulcer rebleeding: a multicentre, multinational, randomized trial.

BACKGROUND: Controlled pantoprazole data in peptic ulcer bleeding are few. AIM: To compare intravenous (IV) pantoprazole with IV ranitidine for bleeding ulcers. METHODS: After endoscopic haemostasis, 1256 patients were randomized to pantoprazole 80 mg+8 mg/h or ranitidine 50 mg+13 mg/h, both for 72 h. Patients underwent second-look endoscopy on day 3 or earlier, if clinically indicated. The primary endpoint was an overall outcome ordinal score: no rebleeding, rebleeding without/with subsequent haemostasis, surgery and mortality. The latter three events were also assessed separately and together. RESULTS: There were no between-group differences in overall outcome scores (pantoprazole vs. ranitidine: S0: 91.2 vs. 89.3%, S1: 1.5 vs. 2.5%, S2: 5.4 vs. 5.7%, S3: 1.7 vs. 2.1%, S4: 0.19 vs. 0.38%, P = 0.083), 72-h clinically detected rebleeding (2.9% [95% CI 1.7, 4.6] vs. 3.2% [95% CI 2.0, 4.9]), surgery (1.9% [95% CI 1.0, 3.4] vs. 2.1% [95% CI 1.1, 3.5]) or day-3 mortality (0.2% [95% CI 0, 0.09] vs. 0.3% [95% CI 0, 1.1]). Pantoprazole significantly decreased cumulative frequencies of events comprising the ordinal score in spurting lesions (13.9% [95% CI 6.6, 24.7] vs. 33.9% [95% CI 22.1, 47.4]; P = 0.01) and gastric ulcers (6.7% [95% CI 4, 10.4] vs. 14.3% [95% CI 10.3, 19.2], P = 0.006). CONCLUSIONS: Outcomes amongst pantoprazole and ranitidine-treated patients were similar; pantoprazole provided benefits in patients with arterial spurting and gastric ulcers.

Bioassay of inhibitory activity of gastrone on basal HCl secretion in rats with chronic gastric fistula.

The authors evaluated the applicability of the rat with gastric fistula to the bioassay of gastrone, endogenous inhibitor of gastric acid secretion and the role of anticholinergic mechanism in this inhibition. 104 individual bioassays were performed on 25 rats with chronic gastric fistula out of which 34 tests were performed with gastrone, 49 controls with saline and 21 with atropine. In rats serving as their own controls, a statistically significant reduction of the volume of basal gastric secretion and of the basal HCl output by 56 and 59%, respectively, occurred after intravenous administration of 40 mug gastrone B. This was demonstrated in the first 4 h after gastrone and was statistically highly significant (p less than 0.001). There was no significant difference, however, in the concentration of HCl in the gastric juice after gastrone and after saline. The inhibitory effect of gastrone on HCl output at the intravenous dose of 40 mug was greater than that of 0.1 mg/kg atropine intravenously, while that of 50 mug gastrone was about equal to that of 0.4 mg/kg atropine. The gastrone inhibitory activity on gastric acid secretion in rats appears to be unrelated to anticholinergic mechanism. The advantages of the bioassay of gastrone activity using rats with chronic gastric fistula over the rats with pyloric ligation are discussed.