Orthotopic liver transplantation after successful treatment with anti-CD20 monoclonal antibody (rituximab) for severe steroid-resistant autoimmune hemolytic anemia: a case report.

Chronic hepatitis C virus (HCV) infection has been associated with a wide number of immunologic disorders, ranging from clinically silent laboratory abnormalities (eg, autoantibody positivity) to severe systemic diseases (eg, cryoglobulinemic vasculitis). Autoimmune hemolytic anemia (AIHA), due to the production of antibodies against erythrocyte membrane antigens, is an uncommon extrahepatic manifestation in the setting of chronic hepatitis C. Herein we have reported the case of a 57-year-old woman with decompensated HCV-related cirrhosis awaiting orthotopic liver transplantation (OLT) who experienced severe AIHA. After 1 month of treatment with prednisone (1 mg/kg body weight/d), there was no significant amelioration of anemia. Rituximab, an anti-CD20 monoclonal antibody that depletes B-lymphocytes reducing serum immunoglobulins, was initiated (375 mg/m(2) IV, weekly for 4 weeks) with a prompt, sustained increase in hemoglobin. The drug was well tolerated; it did not interfere with the course of the liver disease. Thirty-one months after rituximab therapy with resolution of AIHA, the patient successfully underwent OLT using immunosuppression with tacrolimus and low-dose steroids. The patient was discharged on postoperative day 36. No infectious event occurred in the postoperative period. At 18 months follow-up after OLT, there has been no infectious or hematological event. Our experience supported the safety of rituximab use in patients with advanced HCV-related liver disease before OLT.

Sustained virological responses following standard anti-viral therapy in decompensated HCV-infected cirrhotic patients.

BACKGROUND: Little data is available about predictors of sustained virological response (SVR) during anti-viral therapy of patients with decompensated HCV cirrhosis. AIMS: To determine whether rapid and early virological responses (RVR and EVR) could predict SVR and help optimize treatment in these patients. METHODS: A total of 94 cirrhotics underwent treatment with peg-interferon alfa-2b (1.5 microg/kg weekly) and ribavirin (800/1200 mg daily) for 48 or 24 weeks for genotypes 1/4 or genotypes 2/3, respectively. RESULTS: Overall, SVR was achieved in 33 patients (35.1%), 16% with genotype 1/4 and 56.8% with genotype 2/3 (P < 0.01). At treatment week 4, 34 patients had undetectable HCV-RNA, 10 with genotype 1/4 and 24 with genotype 2/3. Of RVR patients, 24 achieved SVR (70.5%), 6 and 18 with genotypes 1 and non-1. At the multivariate analysis, only EVR, genotypes 2 and 3, and adherence to full course and dosage of therapy retained their independent predictive power, with corresponding ORs of 25.5 (95% CI 3.0-217.3), 4.2 (95% CI 1.2-15.3) and 9.1 (95% CI 2.2-38.0), respectively. CONCLUSION: In decompensated cirrhotic patients, anti-viral therapy with current regimens is feasible and associated with an overall SVR rate of 35.1%. Treatment ought to be pursued among patients who attain an EVR, and maintain a full course and dosage of therapy.

A 5-year prospective study of the late resolution of chronic hepatitis C after antiviral therapy.

BACKGROUND: Persistence of hepatitis C virus (HCV) in serum is assured after any course of antiviral therapy that failed to obtain a sustained virological response. AIM: To evaluate the long-term effect on serum HCV-RNA of a course of pegylated-interferon and ribavirin therapy that was unable to obtain sustained response. METHODS: Serum HCV-RNA was determined at monthly intervals in 68 non-responders, breakthroughs or relapsers and in 52 naïve controls enrolled in a five-year study. RESULTS: Five genotype 2 or 3 patients (one non-responder, three breakthroughs, one relapser) cleared HCV-RNA after the end of therapy or relapse, and remained negative until the end of follow-up. HCV-RNA clearance rate in genotype 2 and 3 non-responders, breakthroughs or relapsers was higher than in controls with the same genotypes (22.7% vs. 0%; log-rank 9.62; P < 0.002). HCV-RNA at the end of treatment or at relapse was <10(5) IU/mL in the five subjects who cleared the virus and <10(4) IU/mL in four of them. None of genotype 1 or 4 subjects cleared HCV-RNA during follow-up. CONCLUSIONS: Late resolution of HCV infection is possible in genotype 2 or 3 patients with low viral load at the end of therapy or at relapse. In these subjects, HCV-RNA monitoring is advisable during the first year after therapy.

Cirrhotic cardiomyopathy.

Decompensated liver cirrhosis is characterized by a peripheral vasodilation with a low-resistance hyperdynamic circulation. The sustained increase of cardiac work load associated with such a condition may result in an inconstant and often subclinical series of heart abnormalities, constituting a new clinical entity known as "cirrhotic cardiomyopathy". Cirrhotic cardiomyopathy is variably associated with baseline increase in cardiac output, defective myocardial contractility and lowered systo-diastolic response to inotropic and chronotropic stimuli, down-regulated beta-adrenergic function, slight histo-morphological changes, and impaired electric "recovery" ability of ventricular myocardium. Cirrhotic cardiomyopathy is usually clinically latent or mild, likely because the peripheral vasodilation significantly reduces the left ventricle after-load, thus actually "auto-treating" the patient and masking any severe manifestation of heart failure. In cirrhotic patients, the presence of cirrhotic cardiomyopathy may become unmasked and clinically evident by certain treatment interventions that increase the effective blood volume and cardiac pre-load, including surgical or transjugular intrahepatic porto-systemic shunts, peritoneo-venous shunts (LeVeen) and orthotopic liver transplantation. Under these circumstances, an often transient overt congestive heart failure may develop, with increased cardiac output as well as right atrial, pulmonary artery and capillary wedge pressures.

[Evaluation of the appropriateness of hospital use: the case of IRCCS Ospedale Maggiore di Milano, Italy]. / Valutazione di appropriatezza sull'utilizzo dell'Ospedale: il caso dell'IRCCS Ospedale Maggiore di Milano.

To measure the level of not appropriated hospital use for some DRG's a Lombardia Region AEP version was applied to two units in the Ospedale Maggiore in Milano. The aims of the study was to evaluate the level of appropriateness in Neurology and Dermatology wards for some DRG's which are at risk to be applied in not appropriated way, to study the reasons of not appropriated use, to educate medical doctors in neurology and dermatology to apply for the right level of care for they patients and to highlight some limits of the Lombardia Regional protocol.

[Evaluation of the urgent outpatient visits in a research and teaching hospital in Milan]. / Valutazione delle prescrizioni ambulatoriali erogate in regime di urgenza differita in un ospedale di insegnamento e ricerca a Milano.

Through a questionnaire it was evaluated the appropriate access for outpatient activities at not urgent level requested by general practitioners in Lombardia Region in a teaching and research hospital in the centre of Milan. The study took place from November 2003 to May 2004. 852 questionnaires were analyzedfor 16 specialties. Without judging the clinical appropriateness of prescriptions, the urgent level at which the visits were requested was, for the most part of them, not appropriated. But the not appropriated prescriptions were 49% of all the visits. In the case of use of inappropriate urgent level of care, patients were sent back to the general practitioner and in the case of right level of emergency patients were scheduled for a visit after some days. Results of the study will send to general practitioners for a righter use of the hospital level of care.

[An atypical bone metastasis of hepatocellular carcinoma: case report and review of the literature]. / Una metastasi ossea atipica in corso di epatocarcinoma: descrizione del caso clinico ed analisi della letteratura.

Bone metastases are a quite frequent complication of hepatocellular carcinoma (HCC). They are a substantial fraction (about 14-28%) of the metastatic locations of this neoplasm. Recent studies are indicative of the clinical usefulness of local therapy of HCC bone metastasis, expecially if they are single locations. The presence of a single bone metastasis does not seem to influence short term prognosis of the primary neoplasm and, furthermore, its treatment by radiation, chemio-embolization or surgery may obtain long-term pain control, without the side effects of analgesic drugs. Most frequently, bone metastases of HCC appear in the spine, femur, humerus or ribs. In the last years, some atypical locations, as jaws, gums and skull, were reported. In this paper, we report the case of a painful bone metastasis of HCC, localized at the second phalanx of the second finger of the right hand. To our knowledge, until now only two cases of HCC metastatic location at the bones of the hand have been reported. The lesion has been treated by surgical ablation, obtaining long-term pain remission and the withdrawal of the analgesic drugs. Few weeks later, another bone metastasis appeared, located at the second phalanx of the third finger of the same hand, indicating in this subject a peculiar "metastatic tropism".

Correlation of MRI liver volume and doppler sonographic portal hemodynamics with histologic findings in patients with chronic hepatitis C.

PURPOSE: The purpose of this study was to correlate portal hemodynamics on sonography and liver volume on MRI with histologic findings in asymptomatic patients with chronic hepatitis C. METHODS: Portal blood flow in the left and right portal branches in 20 healthy volunteers and in 26 patients was measured using Doppler sonography during both fasting and postprandial states. Total liver and right-and left-lobe volumes were determined using MRI. The ratio between portal blood flow and liver volume determined the "portal flow index" of the right and left lobes. RESULTS: We observed a statistically significant difference (p < 0.01) between the volunteers and patients in the mean left-lobe volume (352 +/- 81 cm(3) versus 544 +/- 159 cm(3)) and in the mean left portal flow index (1.1 +/- 0.2 ml/minute/cm(3) versus 0.69 +/- 0.2 ml/minute/cm(3)) as measured before the subjects ate. After a meal, the portal blood-flow volume in the right lobe was similar in the 2 groups but in the left lobe was significantly lower in the patients (p = 0.0009). The left postprandial portal flow index was inversely correlated with the grade of liver fibrosis (r = 0.533). CONCLUSIONS: The left-lobe volume (positive predictive value, 83%; negative predictive value, 72%) and left postprandial portal flow index (positive predictive value, 86%; negative predictive value, 88%) are sensitive indicators of chronic hepatitis. The left postprandial portal flow index may be a useful test for differentiating patients with minimal or no fibrosis from patients with mild to severe fibrosis.

Patent side branches do not affect coronary blood flow in internal thoracic artery-left anterior descending anastomosis: an experimental study.

BACKGROUND: It has been reported that large side branches of internal thoracic artery grafts may steal flow from the coronary circulation. Material an. METHODS: To assess the importance of the side branches, we measured the proximal and distal flow and pressures (mean subclavian artery pressure and mean arterial anastomotic pressure) at baseline and during infusion of adenosine (0.5 mg/kg/min) in 10 Landrace pigs in which an internal thoracic artery-left anterior descending anastomosis was constructed without interruption of the side branches. The difference between proximal and distal flow was considered to represent the blood flow of the internal thoracic artery side branches. Measurements were then repeated after surgical occlusion of all the side branches. RESULTS: At baseline, blood flow of the side branches represented 18% of the total flow in the proximal internal thoracic artery, and this percentage remained constant under the infusion of adenosine, which caused a 220% increase of the cardiac index and a 368% increase of the proximal flow. The infusion reduced the gradient along the left internal thoracic artery (mean subclavian artery pressure-mean arterial anastomotic pressure) from 15 to 10 mm Hg (P =.02) as the result of a lower mean subclavian artery pressure, although the mean arterial anastomotic pressure remained constant. Interruption of all the side branches resulted in a small and not significant increase in distal flow even after adenosine infusion. CONCLUSION: These observations suggest that blood flow in the side branches is minimal either at baseline and under combined systemic and coronary vasodilation. Clinically significant flow steal from the coronary circulation to the internal thoracic artery side branches seems then unlikely.

Time dependence of endothelium-mediated vasodilation by intermittent antegrade warm blood cardioplegia.

BACKGROUND: The technique of intermittent antegrade warm blood cardioplegia (IAWBC) exposes the heart to brief periods of normothermic ischemia. This may impair endothelial function in coronary arteries. METHODS: Three cardioplegic technique were tested in porcine hearts arrested for 32 to 36 minutes and reperfused for 30 minutes: IAWBC, antegrade cold blood cardioplegia (ACBC), and antegrade cold crystalloid cardioplegia (ACCC). In the hearts arrested with IAWBC, three different intervals of ischemia were used: three 10-minute intervals (IAWBC1), two 15-minute intervals (IAWBC2), and one 30-minute interval (IAWBC3). Rings from the coronary arteries were used to evaluate in vitro the contractile responses to U46619 and the relaxant responses to bradykinin, A23187, and sodium nitroprusside. RESULTS: All six groups (treatment groups and control group) displayed similar responses to U46619 (30 nmol/L) and nitroprusside. In the IAWBC1, IAWBC2, AND ACBC groups, endothelium-dependent relaxations to bradykinin and A23187 were preserved compared with controls, whereas those of the ACCC and IAWBC3 groups were significantly impaired (bradykinin: control, 8.72 +/- 0.07; IAWBC1, 8.73 +/- 0.03; IAWBC2, 8.65 +/- 0.05; IAWBC3, 8.30 +/- 0.07 [p < 0.05]; ACBC, 8.50 +/- 0.03; ACCC, 8.25 +/- 0.09 [p < 0.05]; A23187: control, 7.07 +/- 0.08; IAWBC1, 7.07 +/- 0.06; IAWBC2, 7.04 +/- 0.03; IAWBC3, 6.64 +/- 0.01 [p < 0.05]; ACBC, 6.80 +/- 0.05; ACCC, 6.60 +/- 0.08 [p < 0.05]; nitroprusside: control, 6.19 +/- 0.1; IAWBC1, 6.19 +/- 0.07; IAWBC2, 6.03 +/- 0.03; IAWBC3, 6.08 +/- 0.05; ACBC, 6.04 +/- 0.2; ACCC, 6.05 +/- 0.03; all values are expressed as the negative logarithm of the concentration producing 50% of the maximal response). CONCLUSIONS: Myocardial preservation with IAWBC with ischemic intervals of 15 minutes or shorter does not alter the endothelium-dependent relaxation to bradykinin or A23187 in porcine coronary arteries, but these responses are significantly impaired by ACCC and IAWBC with an ischemic interval of 30 minutes.

Pathophysiology of liver circulation with an overview of medical and invasive treatments.

Liver hemodynamics is characterized by a dual venous and portal blood supply whose physiologic variations are particularly evident during digestion. In the normal subject portal blood flow is laminar with the left liver receiving the blood from the small intestine while the left liver is supplied by the blood from the spleen and colon. In pathologic conditions increased arterial blood flow accompanies the decreased portal flow. Portal hypertension in its various forms is the most frequent and important circulatory alteration in chronic liver disease; besides the "organic" obstacles to the hepatic blood flow there are the dynamic mechanisms which regulate the vascular resistance in the microcirculation Therapies which impact on liver circulation are surgical, of interventional radiology and medical, used in the prevention and cure of complications of portal hypertension.

Effects of acute and prolonged administration of propafenone on internal defibrillation in the pig.

Some antiarrhythmic sodium channel blocking drugs have been found to increase the energy necessary for internal defibrillation. Propafenone is a new drug that has been shown to be efficacious in the therapy of supraventricular and ventricular arrhythmias, and is of potential use in patients with defibrillators. The effects of short-term and prolonged propafenone administration on the internal defibrillation threshold (DFT) were determined in 43 pigs randomized to one of four groups: saline infusion (n = 10); propafenone infusion (n = 10); placebo administration for 8 days (n = 10); or propafenone administration for 8 days (n = 13). Two mesh electrodes were sutured on the right lateral and left lateral epicardial surface and current was delivered from the right electrode to the left electrode. Triplicate DFTs were obtained before and at 40 and 80 minutes after infusion of drug or placebo. In pigs receiving long-term administration, after baseline DFTs were obtained the electrodes were removed and the chest was closed. Following 8 days of drug or placebo administration, DFTs were redetermined. No changes were observed in the short- or long-term control groups. DFTs were lower after propafenone administration: either short-term infusion (20 +/- 6.2 joules at baseline; 15.6 +/- 5 joules at 40 minutes, p less than 0.05; 10.2 +/- 6 joules at 80 minutes, p less than 0.001) or long-term administration (17.8 +/- 2.6 joules at baseline versus 12 +/- 3.2 joules on drug, p less than 0.002). Decreased ventricular cycle lengths were found with acute administration of propafenone. Three pigs died during long-term administration of propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison between two versus three patches single pulse shock defibrillation in pigs.

The aim of the study was to test the hypothesis that defibrillation with a single pulse shock can be obtained at lower energy using three epicardial patches configuration (one cathode and two anodes) instead of the conventional two patches. The total surface area of the two- and three-patches configuration was the same (10 cm2 vs 9.9 cm2). Epicardial spatial configuration was planned by using a computerized heart model. In ten anesthetized open-chest pigs, ventricular fibrillation was induced by using AC current through the mesh plaque epicardial custom-designed electrodes, and the minimum energy requirement for defibrillation was determined 15 seconds after the onset of stable ventricular fibrillation. Results were as follows (mean +/- standard deviation): Defibrillation Threshold 16 +/- 9 J 9 +/- 5 J P less than 0.01 CONCLUSIONS: three epicardial patches configuration significantly reduces energy requirements for defibrillation compared with two patches when single pulse shock is used.

Intravenous propafenone reduces energy requirements for defibrillation in pigs.

The effect of antiarrhythmic drugs on defibrillation threshold have become an important issue with the increasing use of the automatic implantable cardioverter defibrillator (AICD). In several reports antiarrhythmic therapy has been found to affect the energy required for defibrillation; the present study examined the effects of intravenous propafenone on defibrillation threshold in open chest, anesthetized pigs. Twenty health pigs were studied; 10 pigs free from any drugs (Group 1) and 10 pigs after a constant iv infusion of 0.04 mg/kg/min of propafenone (Group 2). Defibrillation threshold was 21 +/- 5, 20 +/- 5, 21 +/- 6, 19 +/- 4 and 19 +/- 6 J in Group 1 and 20 +/- 7, 18 +/- 9, 15 +/- 5, 14 +/- 7, 9 +/- 6 J in Group 2, respectively at 20, 40, 60, 80 min (p value respectively NS, NS, less than 0.05, less than 0.01, less than 0.001). We conclude that intravenous propafenone reduces the energy requirements for defibrillation in experimental animals.

Surgical correction of congenital left coronary-pulmonary artery fistula and rheumatic mitral valve disease. Case report.

A 56-year-old woman with stenosis and incompetence of the mitral valve and clinical signs of congestive heart failure was found to have a communication between the left anterior descending coronary artery and the pulmonary trunk. A mitral valve prosthesis was inserted and the fistula was closed from within the pulmonary artery.

Somatostatin and peripheral blood flow in man.

Somatostatin (SS), a physiological substance which inhibits secretion of GH, TSH, glucagon and insulin, was evaluated as a vasoactive agent. In normal and arteriopathic subjects SS was administered intravenously by bolus for 3 minutes and by infusion for 30 minutes. Rheography and plethysmography of lower limbs were performed before, during and after somatostatin administration. A marked improvement of blood flow, provoked by somatostatin, was observed. A reduction of heart rate was also observed. Some hypotheses about the mechanism with which SS acts upon peripheral circulation are discussed.

Visual evoked potential recordings in hepatic encephalopathy and their variations during branched chain amino-acid treatment.

In fourteen subjects with various stages of hepatic encephalopathy (HE), Visual Evoked Potential (VEP) recording and blood ammonia (NH3), octopamine (OCT) and phenylethanolamine (PEA) determinations were performed before and during a four-day treatment with branched chain amino acid (BCAA) i.v. infusion. All the subjects with HE showed significant basal VEP alterations, namely an increased latency and a lowered amplitude of the P100 wave, in comparison with a control group of 26 normal subjects. A significant improvement in P100 wave amplitude occurred just about 60' after the beginning of BCAA infusion, while P100 latency was still unaffected, as were OCT, PEA and NH3 levels. After the fourth day of BCAA treatment, both P100 wave amplitudes and latencies were strongly improved, together with OCT, PEA and NH3 levels. VEP improvements seemed to be well correlated with HE clinical evolution, and were able to detect modifications of central nervous system reactivity earlier than serum parameters.