Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites.

The effects of the acute administration of arterial vasoconstrictors on renal plasma flow (RPF) and urinary sodium excretion (UNaV) in cirrhotic patients with ascites with or without hepatorenal syndrome (HRS) are still controversial. As a consequence, vasoconstrictors are not actually used in the treatment of renal sodium retention or HRS in these patients, regardless of the several lines of evidence suggesting that these renal functional abnormalities are related to a marked arterial vasodilation. The lack of an orally available effective arterial vasoconstrictor probably represents a further reason for this omission. Consequently, the present study was made to evaluate the acute effects of the oral administration of midodrine, an orally available -mimetic drug, on systemic and renal hemodynamics and on UNaV in cirrhotic patients with ascites. Mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), systemic vascular resistance (SVR), left forearm blood flow (LFBF), left leg blood flow (LLBF), RPF, glomerular filtration rate (GFR), UNaV, plasma renin activity (PRA), plasma concentration of antidiuretic hormone (ADH), and the serum levels of nitrite and nitrate (NOx) were evaluated in 25 cirrhotic patients with ascites (17 without HRS and 8 with type 2 HRS) before and during the 6 hours following the oral administration of 15 mg of midodrine. During the first 3 hours after the drug administration, a significant increase in MAP (89.6 +/- 1.7 vs. 81.80 +/- 1.3 mm Hg; P < .0001) and SVR (1, 313.9 +/- 44.4 vs. 1,121.2 +/- 60.1 dyn . sec . cm-5; P < .0001) accompanied by a decrease in HR (69 +/- 2 vs. 77 +/- 3 bpm; P < .005) and CI (2,932.7 +/- 131.4 vs. 3,152.5 +/- 131.4 mL . min-1 . m2 BSA; P < .0025) was observed in patients without HRS. No change was observed in LFBF and LLBF. The improvement in systemic hemodynamics, which was also maintained during the the 3- to 6-hour period after midodrine administration, was accompanied by a significant increase in RPF (541.5 +/- 43.1 vs. 385.7 +/- 39.9 mL . min-1; P < .005), GFR (93.1 +/- 6.5 vs. 77.0 +/- 6.7 mL . min-1; P < .025), and UNaV (92.7 +/- 16.4 vs. 72.2 +/- 10.7 microEq . min-1; P < .025). In addition, a decrease in PRA (5.33 +/- 1.47 vs. 7.74 +/- 2.17 ng . mL-1 . h; P < .05), ADH (1.4 +/- 0.2 vs. 1.7 +/- 0.2 pg . mL-1; P < .05), and NOx (33.4 +/- 5.0 vs. 49.3 +/- 7.3 micromol-1; P < .05) was found. In patients with HRS, the effects of the drug on the systemic hemodynamics was smaller and shorter. Accordingly, regardless of a significant decrease in PRA (15.87 +/- 3.70 vs. 20.70 +/- 4.82 ng . mL-1 . h; P < .0025) in patients with HRS, no significant improvement was observed in RPF, GFR, or UNaV. In conclusion, the acute oral administration of midodrine is associated with a significant improvement in systemic hemodynamics in nonazotemic cirrhotic patients with ascites. As a result, renal perfusion and UNaV also improve in these patients. By contrast, midodrine only slightly improves systemic hemodynamics in patients with type 2 HRS, with no effect on renal hemodynamics and renal function.

Q-T interval prolongation in liver cirrhosis. Reversibility after orthotopic liver transplantation.

The aim of this work was to study the prevalence of Q-T prolongation in patients with liver cirrhosis and the modifications of the Q-T interval after liver transplantation. Q-T interval corrected for heart rate (QTc) and dispersion of Q-T interval were evaluated in 75 cirrhotic patients and in 24 controls by means of a 12-lead electrocardiogram. In addition, 15 patients were evaluated before and after liver transplantation. Forty-five patients (60%) had a prolonged Q-Tc. Compared with controls, both patients with alcoholic and non alcoholic cirrhosis had increased Q-Tc (414 +/- 28 msec1/2, 463 +/- 31 and 444 +/- 32 respectively; p < 0.001 and < 0.001); Q-Tc was significantly higher in alcoholic than in non-alcoholic cirrhosis (p < 0.02). Q-T dispersion was normal in cirrhotics. No correlation was found between Q-Tc interval and severity of the cirrhosis, haemodynamic variables (stroke volume, cardiac output) and s-calcium and potassium concentrations. After transplantation, Q-Tc decreased significantly (415 +/- 26 msec1/2 vs 449 +/- 31; p < 0.0001) returning to the values of the normal subjects, but no modification of the Q-T dispersion was observed. These data show that 1) prolongation of Q-T interval is frequent in cirrhosis, being higher in alcoholic than in non-alcoholic cirrhosis, 2) is not related to the severity of the disease, and 3) is reversible after transplantation.

[Benign ulcers of the cecum]. / Le ulcere benigne del cieco.

Benign ulceration of the cecum is an uncommon lesion that was originally described by Cruveilhier in 1832. Etiology is unknown and symptomatology not pathognomonic. Pre-operative and intraoperative diagnosis is rare and difficult. Definitive diagnosis is usually obtained by histologic evaluation of the surgical specimen after a right hemicolectomy performed for a suspect of a neoplasm of the cecum. The authors present 7 cases of cecal ulcers and suggest that preoperative diagnosis may be due after a colonoscopy with biopsy. This examination may be performed only in that cases that appear without symptoms of acute abdomen. The authors suggest also to perform right hemicolectomy.

Left ventricular diastolic function in liver cirrhosis.

BACKGROUND: Left ventricular systolic abnormalities have been reported in liver cirrhosis (LC). Diastolic function in cirrhotics, on the contrary, does not seem to have been studied so far. METHODS: Diastolic function was evaluated in 42 cirrhotic patients and in 16 controls by means of Doppler echocardiography. RESULTS: Compared with the controls, cirrhotics had increased left ventricular end-diastolic and left atrial volume, stroke volume, late diastolic flow velocity (peak A) (71 + or - 17 cm/sec versus 56 +/- 18; p <0.01), time from onset of mitral inflow to the early peak (time E) (86 + or - 11 msec versus 72 +/- 14; p < 0.003), and deceleration time (DT) (194 +/- 40 msec versus 159 +/- 27; p < 0.001) and decreased ratio of peak E to peak A filling velocities (1.02 +/ - 0.35 versus 1.22 +/- 0.25; p < 0.02). Patients with tense ascites had a higher E/A ratio (p < 0.03) and a shorter DT (p < 0.03) than patients with mild or no ascites. CONCLUSIONS: The impaired left ventricular relaxation in the presence of high stroke volume suggests a myocardial involvement in LC. The pseudo normalization of the E/A ratio and DT in patients with tense ascites could reflect loading conditions masking the relaxation abnormality.

[Phyllodes tumor of the breast]. / Il tumore filloide della mammella.

The diagnosis of benign, malignant or borderline phylloides tumor of the breast is based on a combination of clinical and histological features but the biological behavior of this neoplasm is not often predictable: the most important indicators of malignant behavior are underscored. Only a few patients with malignant or borderline lesions develop distant metastasis; local recurrences do not appear to effect survival: as a consequence, wide resection should to be primary treatment and axillary dissection is not worthwhile.

Prognostic usefulness of hepatic vein catheterization in patients with cirrhosis and esophageal varices.

Clinical and anamnestic data, Pugh score, and size of esophageal varices were obtained in 129 cirrhotics. Hepatic vein catheterization was performed to measure hepatic venous pressure gradient (HVPG), indocyanine green (ICG) intrinsic hepatic clearance, and hepatic plasma flow. During a follow-up period of up to 60 months, 44 patients experienced gastrointestinal bleeding and 54 died. Applying Cox regression analysis, ICG intrinsic hepatic clearance, Pugh score, previous variceal bleeding, and HVPG were the only significant prognostic determinants of survival. In addition, Cox's regression analysis showed that HVPG, Pugh score, size of varices, and previous variceal bleeding all contained significant prognostic information regarding risk of gastrointestinal bleeding. The models were validated using a split-sample technique, and prognostic indexes for death and gastrointestinal bleeding were calculated. The prognostic index predicting death had significantly improved prognostic accuracy over a prognostic index calculated excluding the data obtained from hepatic vein catheterization (P less than 0.05). In conclusion, prognostic accuracy in cirrhosis with portal hypertension is significantly improved by information obtained from hepatic vein catheterization.

Evaluation of splanchnic angiography as a prognostic index of survival in patients with cirrhosis.

Prognostic evaluation of advanced liver disease is usually made on the basis of the common clinical and biochemical data included in the Child-Turcotte classification. The aim of this study was to evaluate the contribution of data from splanchnic angiography as a guide to prognosis in patients with cirrhosis. Over an 8-year period 219 patients with cirrhosis were investigated by splanchnic angiography and followed up prospectively. At the end of the study 95 patients had died (43.4%). Median survival time was 68 months. In addition to several clinical and biochemical data, hepatic portal venous perfusion and the presence of caudad hepatofugal veins as assessed by angiography were significant predictors of survival. Incorporating all nonangiographic variables in a Cox's multiple regression analysis, a clinicobiochemical set of prognostic covariates (ascites, s-albumin, gammaglobulins, s-alkaline phosphatase, and sex) was selected. When adding to this model each of the angiographic variables, only portal perfusion resulted in an independent predictor of survival. In conclusion, in cirrhotics the angiographic evaluation of portal perfusion improved the prognostic information obtained from clinical and biochemical data.

[Diagnostic reliability of echography in ureteral lithiasis]. / Attendibilità diagnostica dell'ecografia nella litiasi ureterale.

This article takes into account the diagnostic reliability of ultrasounds (US) in the ureteral lithiasis localisation. A stone has been ultrasonographically localised in 82.3% of 119 patients, this rate rising up to 89.4% in the last 85 consecutive patients. From a clinical point of view, 104 patients presented renal signs, whereas 10 out of them showed an atypical symptomatology, which at first led to a suspicion of acute appendicitis (5), intestinal obstruction (4), acute pancreatitis (1). A stone was accidentally detected in five asymptomatic patients. In 80% of the cases, the stone was situated in the proximal or juxtavesical ureter; in 20%, in the middle or distal ureter. A particular stress is laid in the ultrasonographic follow-up, by which the stone was uncovered in 6 cases, at first considered negative at US. Eight patients had to be referred to treatment with ESWL.

Clinical significance of cholelithiasis in patients with decompensated cirrhosis.

There is general agreement that the prevalence of gallstones in cirrhotics is high (at least twice that in the general population), but the pathogenetic link between cirrhosis and cholelithiasis is still uncertain. The influence of cholelithiasis on survival in cirrhotics is also unknown. During an 8-year period, we observed 90 patients affected by decompensated cirrhosis: 36 of them (40%) turned out by cholecystographic/cholangiographic or ultrasonographic examination to have cholelithiasis. We were not able to demonstrate any correlation between cholelithiasis and sex, age of patients, etiology of cirrhosis, severity of the illness, degree of portal hypertension, previous gastrointestinal bleeding, number of pregnancies, or levels of serum cholesterol, bilirubin, and triglycerides. During the follow-up observation, (range, 1-91 months), 30 patients died. Survival curves analyzed by the log-rank test did not show any difference between patients with or without gallstones. We therefore confirm that cirrhosis is a lithogenic condition, but we were not able to explain the reasons for the close relationship between cholelithiasis and cirrhosis. Gallstones, however, did not affect the survival of these patients.

Lack of effect of verapamil and isosorbide dinitrate on the hepatic clearance of indocyanine green in cirrhosis.

1. Vasodilators are currently under investigation as possible therapeutic agents in the treatment of portal hypertension. Among them calcium-channel antagonists and organic nitrates have been of particular interest. Few and conflicting data, however, have been reported on their effect on liver function. 2. Twenty patients with biopsy-proven alcoholic cirrhosis were studied before and 25-35 min following the acute administration of 5 mg verapamil i.v. (eight patients) or 5 mg isosorbide dinitrate sublingually (12 patients). The plasma clearance of indocyanine green (ICG) and its intrinsic hepatic clearance were used as indices of liver function. Seven further patients were investigated before and after a placebo infusion according to the same methodology. 3. No significant change in ICG kinetics was found after verapamil or isosorbide dinitrate.

Indocyanine green intrinsic hepatic clearance as a prognostic index of survival in patients with cirrhosis.

The prognostic value of quantitative liver function tests in patients with cirrhosis is not clearly established. Indocyanine green intrinsic hepatic clearance (ICG-IHC) is a quantitative liver function parameter independent of liver blood flow, which was shown to correlate strictly with the Child-Turcotte-Pugh (CTP) classification of severity of liver disease. Few data are available on its prognostic value. One hundred and five patients with cirrhosis were studied. ICG-IHC was measured according to the 'sinusoidal perfusion' model. Median ICG-IHC in the whole series was 374 ml/min (interquartile range: 214-496 ml/min). During follow-up (mean 31 months; max. 48 months) 38 patients died. The probability of survival was lower in patients with ICG-IHC lower than 300 ml/min (35% at 48 months) than in patients with ICG-IHC between 300 and 1000 ml/min (70%), or with ICG-IHC over 1000 ml/min (80%) (P = 0.02). Also s-albumin (P less than 0.01), ascites (P = 0.001) and CTP class (P less than 0.001) were significant predictors of survival. On incorporation of age, sex, etiology of cirrhosis, ICG-IHC, s-albumin, s-bilirubin, prothrombin index, ascites and encephalopathy, into a multiple regression analysis according to the Cox's model, the results showed only ascites and s-albumin to be independent significant predictors of survival, while ICG-IHC was not among the covariates independently predictive of survival. When CTP class was added to the investigated covariates, the results showed it as the only independent predictor of survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic changes of systemic, hepatic, and splenic circulation following triglycyl-lysin-vasopressin administration in alcoholic cirrhosis.

Triglycyl-lysin-vasopressin is a long-acting vasopressin derivative which is under consideration for the treatment of acute variceal bleeding in cirrhosis. However, its splanchnic hemodynamic effects have not been investigated thoroughly. In 11 patients with alcoholic cirrhosis, systemic and splanchnic hemodynamics were evaluated before and 20-40 min after intravenous administration of 2 mg triglycyl-lysin-vasopressin. Following the drug administration, heart rate decreased by 10% and cardiac index by 22% on the average, respectively; mean arterial pressure increased by 14% and systemic vascular resistence index by 48%. Hepatic venous pressure gradient showed a marked and persistent fall, averaging 31%. Hepatic and splenic blood flow decreased by 31% and 56%, respectively. A significant correlation was found between the decrease in hepatic venous pressure gradient and in splenic blood flow. By contrast, the decrease in the hepatic venous pressure gradient was not significantly correlated to the decrease in hepatic blood flow or in cardiac index. We conclude that in patients with alcoholic cirrhosis, triglycyl-lysin-vasopressin decreases portal pressure as well as hepatic and splenic blood flows. The decrease in portal pressure was due to the decrease in splanchnic blood inflow and not to the decrease in cardiac index.

The calcium-channel blocker, verapamil, does not improve portal pressure in patients with alcoholic cirrhosis.

1. Recently the calcium-channel blocker, verapamil, has been reported to decrease portal pressure in rats with experimental cirrhosis and in patients with liver cirrhosis. 2. In eight patients with alcoholic cirrhosis the effect of verapamil (5 mg i.v.) on systemic and splanchnic haemodynamics was investigated. 3. Mean arterial pressure, wedged hepatic venous pressure, hepatic venous pressure gradient, and verapamil plasma concentrations were measured before and at 10, 20, 30 min following 5 mg i.v. administration of verapamil. At 30-40 min cardiac output, systemic vascular resistance and hepatic blood flow were also measured. 4. Verapamil plasma concentrations averaged 47.9 +/- 52.0, 36.5 +/- 36.3, 31.3 +/- 33.9 ng ml-1 at 10, 20, 30 min respectively: mean arterial pressure and systemic vascular resistance decreased significantly (-9% and -14% respectively), and cardiac index increased significantly (+8%). Wedged hepatic venous pressure and hepatic venous pressure gradient remained unchanged, variations never exceeding 0.2 kPa. Hepatic blood flow increased significantly by 12%. 5. These results show that i.v. administration of 5 mg verapamil does not decrease portal pressure in alcoholic cirrhosis. This lack of effect is probably the consequence of a balance between decrease in porto-hepatic vascular resistance and increase in splanchnic blood inflow.

Long-term effect of nadolol on quantitative liver function tests in patients with cirrhosis.

Nadolol, a non-cardioselective beta adrenoreceptor blocking agent, has been reported to decrease portal pressure without affecting liver function in cirrhotic patients treated for 1 month. There were no data about the long-term effects of nadolol on liver function. In 11 patients with cirrhosis and portal hypertension galactose eliminating capacity, aminopyrine metabolic capacity, ICG clearance and IGC intrinsic hepatic clearance according to the "parallel tube" model were measured before and after 6 months of treatment with nadolol at a dose reducing resting heart rate by approximately 25%. No significant variation in any of these parameters was found. Thus 6 months of continuous oral administration of nadolol did not further impair liver function in cirrhotics.

Verapamil pharmacokinetics and liver function in patients with cirrhosis.

In seven patients with liver cirrhosis, verapamil plasma levels were measured in blood drawn simultaneously from the hepatic vein and from an artery during the post-distributive phase after an intravenous bolus infusion of 5 mg of verapamil. In addition the hepatic plasma flow was measured using the indocyanine-green constant infusion technique. From these data the verapamil hepatic clearance and verapamil intrinsic clearance were calculated. The verapamil hepatic clearance was 423 +/- 92 ml/m, the hepatic plasma flow was 819 +/- 318 ml/m, and the verapamil intrinsic clearance was 1431 +/- 961 ml/m. As compared to values reported in the literature, a decrease of the verapamil hepatic clearance by 50% approximately was found, while the hepatic plasma flow was in the normal range and the verapamil intrinsic clearance was reduced by 75%. These data show that in patients with cirrhosis the decrease in verapamil clearance is due to an impairment in the capacity of the liver to remove the drug, and not to a decrease in liver perfusion.

Long-term effects of beta-adrenergic blockade with nadolol on hepatic and renal haemodynamics and function in cirrhotics.

Non-cardioselective beta-blockers are used for prevention of re-bleeding from oesophageal varices in cirrhotics with portal hypertension. Nadolol, a non-cardioselective beta-blocker with a low liposolubility and a low hepatic metabolism, has been demonstrated to decrease portal pressure in cirrhotic patients. Since cirrhotics need long-term treatment, we investigated long-term effects of beta-adrenergic blockade with nadolol on hepatic and renal haemodynamics and function in a group of patients with cirrhosis and portal hypertension. In 19 patients with cirrhosis, after one and six months of treatment with nadolol hepatic venous pressure gradient showed a significant and persistent decrease, averaging 19% and 22%, respectively. Hepatic function and renal haemodynamics and function remained unaffected. Oesophageal varices severity was lowered in 11/19 patients after one month, in 9/16 after six months, in 8/14 after 12 months and in 5/10 after 18 months. Our results showed that, also after long-term treatment, nadolol decreases portal pressure and, in approximately 50% of patients, oesophageal varices severity, without side-effects on liver and renal function.

Effects of isosorbide dinitrate on portal hypertension in alcoholic cirrhosis.

It has recently been reported that vasodilators lower portal pressure in patients with cirrhosis. This effect, however, is not definitively proven. The effect of isosorbide dinitrate (5 mg sublingually) on splanchnic and systemic hemodynamics was investigated in 13 patients with alcoholic cirrhosis and portal hypertension. The administration of isosorbide dinitrate reduced hepatic venous pressure gradient by 34% (P less than 0.001), mean arterial pressure by 30% (P less than 0.001), cardiac index by 17% (P less than 0.001) and systemic vascular resistance by 11% (P = 0.05). Hepatic blood flow was not affected by the treatment. Significant correlations were found between the decrease in hepatic venous pressure gradient and that of cardiac index (P less than 0.05) and mean arterial pressure (P less than 0.05). These data indicate that isosorbide dinitrate lowers portal pressure in patients with cirrhosis. Decrease in cardiac output, rise in splanchnic arterial vascular resistance and decrease in porto-hepatic resistance seem to participate in determining the effect.

Effect of nadolol on liver haemodynamics and function in patients with cirrhosis.

Beta-adrenoceptor blockers used in the medical management of portal hypertension decrease liver blood flow. The sporadic onset of hepatic encephalopathy during propranolol treatment was ascribed to this decrease. The aim of the present study was to evaluate the effect of chronic treatment with nadolol on liver blood flow and liver function. Nadolol, a non-cardioselective beta-adrenoceptor blocker, has been reported to be as powerful as propranolol in decreasing portal pressure. Before and after 1 month of treatment with nadolol at a dose reducing heart rate by 25%, in 15 cirrhotic patients with portal hypertension, the following parameters were determined: hepatic venous pressure gradient, hepatic blood flow, galactose eliminating capacity, aminopyrine metabolic activity, ICG clearance and intrinsic hepatic clearance. Hepatic venous pressure gradient and hepatic blood flow were decreased by nadolol. However liver function was not affected by the drug. We conclude that, despite a lowered hepatic blood flow, liver function is not affected by 1 month of nadolol treatment.