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Biomedical subjects

L Bolondi

Publications and source records attributed to L Bolondi.

At least 55 records · Page 3Linked to original sources

Systemic and splanchnic hemodynamic changes after liver transplantation for cirrhosis: a long-term prospective study.

The effect of orthotopic liver transplantation (OLT) on the systemic and splanchnic hemodynamic alterations of cirrhosis is still largely unknown. The aim of this study was to prospectively investigate the long-term changes induced by OLT on several hemodynamic parameters. In 28 patients undergoing OLT for cirrhosis, the following parameters were measured before surgery and subsequently at 6-month intervals (mean follow-up period, 17 months): cardiac index, mean arterial pressure (MAP), heart rate, total peripheral resistance (TPR), portal vein flow velocity and flow volume, spleen size, and Doppler ultrasound resistance or pulsatility indexes (RI or PI) in the: 1) interlobular renal, 2) superior mesenteric, 3) splenic, and 4) hepatic arteries. The same parameters were measured in 10 healthy controls. After OLT, cardiac index and heart rate significantly decreased (P <.01), while MAP and TPR increased (P <.001), so that any significant difference from controls disappeared. Renal RI progressively decreased, achieving a significant reduction (P <.05) to normal values at the 12th month of follow-up. Portal flow velocity and hepatic and splenic RI returned to values not significantly different from controls. Portal flow volume increased over normal values after OLT (P <.001), and SMA PI, lower than normal before OLT, did not show any statistically significant increase thereafter. Spleen size decreased significantly, but persisted to be larger than in controls. In conclusion, systemic, renal, and most, but interestingly not all, splanchnic circulatory alterations of cirrhosis are restored to normal after OLT.

Blood Flow Velocity↗

Doppler evaluation of the effects of pharmacological treatment of portal hypertension.

The splanchnic pharmacodynamic effects of the drugs used for the treatment of hemorrhagic complications of portal hypertension were poorly clarified until some years ago. The introduction of Doppler ultrasound provided a powerful tool to investigate such hemodynamic effects and brought new insights in this field. The present article reviews the pharmacodynamics of the substances used in the treatment of portal hypertension, with particular regard to the effects assessable by duplex Doppler ultrasonography.

Adrenergic Agents↗

Imbalance of IL-1 beta and IL-1 receptor antagonist mRNA in liver tissue from hepatitis C virus (HCV)-related chronic hepatitis.

Increased levels of IL-1 beta and IL-1 receptor antagonist (IL-1Ra) have been found in serum of patients with chronic liver diseases, although their expression in liver tissue has not been extensively investigated. The aim of this study was therefore to examine the relationship between IL-1 beta and IL-1Ra at tissue level in patients with HCV-related chronic active hepatitis (CAH) of varying degrees of severity. IL-1 beta and IL-1Ra mRNA expression was investigated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 31 patients with CAH of varying severity (classified as minimal/mild in 13 cases and moderate/severe activity in 18 cases) and in 12 control subjects. Quantitative evaluation of IL-1 beta and IL-1Ra corresponding bands was performed by densitometric image analysis, and expressed in arbitrary units. The 12 controls expressed a similar pattern with a mean IL-1 beta/IL-1Ra ratio of 1.03 (1.03 +/- 0.15 (mean +/- s.e.m.), median 0.92, range 0.71-1.45). Minimal/mild activity CAH showed a prevalence of IL-1Ra mRNA expression (1.14 +/- 0.64, median 0.43, range 0-8.75) when compared with controls (0.27 +/- 0.04, median 0.23, range 0.11-0.45) and with moderate/severe activity CAH (0.20 +/- 0.04, median 0.12, range 0-0.67; P = 0.01). Since IL-1 beta expression was similar in the three groups, a significantly different IL-1 beta/IL-1Ra ratio emerged between controls, patients with moderate/severe CAH (2.22 +/- 0.48, median 2.76, range 0-6.12) and those with minimal/mild activity CAH (0.62 +/- 0.15, median 0.5, range 0-1.58, P = 0.005). Patients with higher grades of fibrosis showed a higher IL-1 beta/IL-1Ra ratio (2.49 +/- 0.56, median 2.15, range 0.35-6.12) in comparison with lower grade fibrosis (1.06 +/- 0.30, median 0.59, range 0.03-4.50) and control patients (P = 0.01). These results suggest that an imbalance between IL-1 beta and IL-1Ra, at the tissue level, may contribute to the pathogenesis and the activity of chronic active hepatitis C.

Adult↗

Pilot study of triple antiviral therapy for chronic hepatitis C in interferon alpha non-responders.

BACKGROUND: No effective therapy exists for interferon non-responding chronic hepatitis C patients. AIMS: Pilot study evaluating the potential efficacy and safety of triple antiviral therapy in interferon-alpha non-responders. PATIENTS AND METHODS: Twenty consecutive adult patients with chronic hepatitis C who had failed to respond to a 6-month course of interferon alpha were randomly assigned to receive a combination of interferon alpha + oral ribavirin (double therapy), or the same combination + oral amantadine (triple therapy), for 6 months. RESULTS: By the end of therapy, normal alanine transaminase (biochemical response) was obtained in 2 out of 10 patients on double therapy but in 7 out of 10 on triple therapy (p < 0.05), and negative serum hepatitis C virus (HCV) RNA (virological response) occurred in 1 out of 10 patients on double therapy but in 7 out of 10 patients on triple therapy (p < 0.01). Six months after therapy, biochemical response was sustained in 1 (double therapy) and 4 patients (triple therapy), respectively, and the virological response was sustained in no patient on double therapy but in 3 patients on triple therapy. CONCLUSIONS: Triple antiviral therapy seems to be able to induce biochemical and virological responses in interferon alpha non-responders with chronic hepatitis C.

Adult↗

Aberrant fragile histidine triad gene transcripts in primary hepatocellular carcinoma and liver cirrhosis.

To determine whether transcriptional alterations of the fragile histidine triad (FHIT) gene play a role in the development and progression of human hepatocellular carcinoma (HCC) we used reverse transcription-PCR to examine mRNA FHIT expression in 28 paired samples of HCC (24 in cirrhotic and 4 in noncirrhotic livers) and matched noncancerous tissue and in 10 normal livers. We also assessed loss of heterozygosity of the polymorphic D3S1300 microsatellite marker in the intron between exons 5 and 6 of the FHIT gene. Abnormal FHIT transcripts were detected in 13 cases (46.4%): 10 in the cancerous tissue only, 1 with the same pattern in both cancerous and matched noncancerous tissue, and 2 in the noncancerous tissue only. The four HCCs that arose in noncirrhotic liver all showed abnormal FHIT transcripts. No alterations were found in normal livers. Sequence analysis of abnormally sized transcripts revealed that they were generated by the fusion of exons 3 or 4 with exons 8 or 9. Among the cancerous specimens, one case showed only an abnormal sized transcript derived from the fusion of exons 4 and 9 in the absence of any normal-sized transcript, and another case showed deletion of a sequence comprised between nucleotides -35 and 399 resulting in an exon 4-9 fusion not respecting the exons' bounds. Loss of heterozygosity was found in two cases with abnormal FHIT transcripts and in only one case with normal transcript. Patients with aberrant FHIT transcripts showed a significantly higher relapse rate and shorter recurrence time (P = 0.001). This could be related to a primary genomic instability affecting particularly susceptible regions like FRA3B and could be associated with an increasing risk of recurrence without involving a causative role.

Acid Anhydride Hydrolases↗

Duplex Doppler findings in splenic arteriovenous fistula.

Splenic arteriovenous fistula (AVF) is a rare cause of portal hypertension. An early diagnosis is crucial because lethal complications may occur if the disease is not treated. We report a case of AVF in a noncirrhotic patient in whom the diagnosis was made by duplex sonography. This technique can differentiate between AVF and other, more common vascular abnormalities in the left upper quadrant in patients with portal hypertension. Duplex sonography can therefore be recommended as the first imaging approach in this population.

Arteriovenous Fistula↗

Portohepatic vascular pathology and liver disease: diagnosis and monitoring.

A number of diseases alter the normal pathophysiology of the portohepatic vascular system. The impact of these changes depends on the severity of the disease and the involvement of the entrahepatic vasculature. Cirrhosis of the liver is not a vascular disease but the effects on the liver architecture result in severe disease often accompanied by hepatic vascular changes. Alcohol abuse and viral infections are the most common causes of cirrhosis. Portal hypertension (PHT) is one of the most frequently seen sequelae of liver cirrhosis. It results in the formation of porto-systemic collateral channels which may lead to varices and hemorrhage. Primary liver cancer is also strongly associated with liver cirrhosis. Hepatocellular carcinoma (HCC) is the most common liver cancer seen in patients with cirrhosis. There are four types of HCC based on its growth patterns: infiltrative, expansive, mixed and diffuse. Raised plasma levels of alpha-fetoprotein are a characteristic of HCC. However, this marker is unreliable in patients with smaller tumors. Ultrasound is an inexpensive, non-invasive and safe diagnostic technique used to detect portal vein changes in PHT and to identify HCC lesions in the liver. Grey scale ultrasound reveals the portal vein changes and the portal-systemic collaterals which typify PHT. The technique is most useful for diagnosis or confirmation of moderate to severe disease. HCC nodules have characteristic ultrasound patterns which help in differential diagnosis. Doppler ultrasound provides functional as well as anatomical information about blood flow in the liver and is especially useful in detecting HCC and the abnormal blood vessel architecture which surrounds a tumor. However, despite their usefulness, both imaging techniques have limitations which may be improved by the use of echo-enhancing agents. Levovist(R) is a galactose-based microbubble echo-enhancing agent which has an excellent safety profile and utility in enhancing ultrasound images of the liver. It markedly improves diagnostic confidence and reduces the percentage of non-diagnostic ultrasound scans in patients with abnormal liver pathologies. The use of echo-enhanced ultrasound to diagnose liver disease may obviate the need for more expensive and invasive diagnostic procedures.

Blood Flow Velocity↗

Duplex-Doppler evaluation of the effects of propranolol and isosorbide-5-mononitrate on portal flow and splanchnic arterial circulation in cirrhosis.

BACKGROUND: A decrease in portal flow is an important pharmacological effect of drugs used for the prophylaxis of variceal bleeding. AIM: To assess the acute and chronic effects of propranolol, and the effect of the acute addition of isosorbide-5-mononitrate, on splanchnic circulation. METHODS: Measurements of portal blood flow volume (PBFV) and of Doppler ultrasound pulsatility index of the superior mesenteric, femoral and interlobar renal arteries were performed in 10 cirrhotic patients with varices at baseline, 90 min after propranolol or placebo, after 30 days of chronic propranolol treatment and 45 min after the addition of isosorbide-5-mononitrate. RESULTS: The mean PBFV was significantly lower at all times than at baseline, with the greatest mean percentage decrease achieved after the addition of isosorbide-5-mononitrate (> or = 20% in all patients). Acute changes, however, did not predict the chronic effects in many patients. Isosorbide-5-mononitrate significantly increased the mesenteric and femoral pulsatility indices, whereas no significant change was observed in the kidney. CONCLUSIONS: Propranolol significantly decreases PBFV, but chronic effects cannot be reliably predicted by the acute change. All patients achieved a decrease in PBFV of > or = 20% after the acute addition of isosorbide-5-mononitrate to chronic propranolol treatment.

Adrenergic beta-Antagonists↗

Superior mesenteric artery impedance in chronic liver diseases: relationship with disease severity and portal circulation.

OBJECTIVE: The increase of splanchnic blood flow volume in liver cirrhosis is attributed to decreased arterial resistance. The aim of this study was to noninvasively investigate superior mesenteric artery impedance in patients with chronic liver diseases and to assess its relationship with portal hemodynamics and with clinical parameters. METHODS: Superior mesenteric artery (SMA) pulsatility (SMA-PI) and resistance (SMA-RI) indices and portal vein flow parameters (velocity, volume, and congestion index) were measured by duplex-Doppler ultrasound in 14 patients with chronic hepatitis, in 73 cirrhotics, in 30 liver transplant recipients, and in 31 control subjects. RESULTS: SMA-PI significantly differed among the five groups (p < 0.0001), being lower in cirrhotics (2.55+/-0.70) and transplanted patients (2.77+/-0.69) than in chronic hepatitis (3.28+/-0.57) and control subjects (3.42+/-0.92). SMA-PI was lower in ascitic cirrhosis (2.40+/-0.71) than in compensated cirrhosis (2.71+/-0.70) (p < 0.01) and in cirrhotics with large varices (2.30+/-0.67) than in those without varices (2.75+/-0.65) (p < 0.05). Moreover SMA-PI correlated with numeric Child-Pugh score (r=-0.28) and portal vein congestion index (r=-0.36). CONCLUSION: Hyperdynamic splanchnic circulation, noninvasively assessed by a decrease of mesenteric artery impedance, occurs in cirrhosis since the early stage of the disease and tends to worsen in relation to liver failure and the severity of portal hypertension. Furthermore, the persistent SMA-PI decrease in transplant recipients suggests a consistent contribution to this circulatory alteration from a patent portosystemic collateral circulation.

Adult↗

A case of extracranial vertebral artery dissection with spontaneous recovery Diagnosis and follow-up by duplex and color Doppler.

A 47-year-old women developed an acute vestibular syndrome with a peripheral facial palsy not associated with any trauma. Magnetic resonance imaging showed an ischemic lesion in the territory of the posterior inferior cerebellar artery. Color Doppler ultrasonography detected an occlusion of the right vertebral artery and dissection of the artery was confirmed by a subsequent angiography. During follow-up Duplex-Doppler allowed a non-invasive monitoring of recanalization of the occluded artery. Copyright 1997 Elsevier Science Ireland Ltd.

Journal Article↗

What is the criterion for differentiating chronic hepatitis from compensated cirrhosis? A prospective study comparing ultrasonography and percutaneous liver biopsy.

BACKGROUND/AIMS/METHODS: The diagnosis of cirrhosis is currently based on percutaneous liver biopsy, although this procedure may give rise to false negative results. This prospective study blindly investigates the accuracy of an ultrasonographic score, derived from liver, spleen and portal vein features, in predicting the final diagnosis in 212 patients with compensated chronic liver disease undergoing percutaneous liver biopsy. RESULTS: Taking biopsy as the standard, the ultrasonographic score differed significantly between chronic hepatitis (39+/-33) and cirrhosis (100+/-35) (p<0.0001). Discriminant analysis with stepwise forward selection of the variables identified liver surface nodularity and portal flow velocity as independently associated with the diagnosis of cirrhosis (p<0.005), and a score based on these two variables correctly identified cirrhosis in 82.2% of cases. One or both of these abnormalities were also found in 27/32 patients who were diagnosed as having cirrhosis at ultrasound, but were not cirrhotic histologically. Eight of these 32 cases developed signs of decompensated liver disease and/or portal hypertension in the subsequent 6-month follow-up, thus supporting the diagnosis of cirrhosis. CONCLUSIONS: Our data suggest that ultrasound is accurate in predicting the final diagnosis in patients with compensated chronic liver disease and may identify cirrhosis even in the absence of a typical histopathological pattern. However, neither percutaneous liver biopsy nor ultrasonography can be assumed to be the definitive criterion for the diagnosis of compensated cirrhosis.

Adolescent↗

Interobserver and interequipment variability of hepatic, splenic, and renal arterial Doppler resistance indices in normal subjects and patients with cirrhosis.

BACKGROUND/AIMS: Doppler arterial resistance indices are used to evaluate alterations in arterial hemodynamics in the liver, spleen, and kidney. The purpose of this study was to determine the interobserver and interequipment variability of hepatic, splenic, and renal arterial Doppler resistance indices, and the influence of a cooperative training program of the operators on the reproducibility of the results. METHODS: In the first part of the study, hepatic (PI-L, RI-L), splenic (PI-S, RI-S), and renal (PI-K, RI-K) pulsatility and resistive indices were measured by echo-color-Doppler in eight control subjects and ten patients with cirrhosis by three operators using three different machines. In the second part of the study, measurements were taken by the three operators in nine controls and nine patients with cirrhosis, after cooperative training, with a single machine. RESULTS: Significant interobserver variability was present for all parameters except RI-L. Significant interequipment variability was present for all parameters except PI-S and RI-S. Only 0-3% of variance was equipment- or operator-related, while 58-72% was patient-related. Hepatic and renal coefficients of variation were similar in patients with cirrhosis and controls, while splenic coefficients of variation were higher in patients with cirrhosis than in controls. After training, differences among operators disappeared for all variables except RI-K, and the operator-related component of variance nearly disappeared for all parameters. CONCLUSIONS: Hepatic, splenic, and renal arterial resistance indices show small but significant interobserver and interequipment variability. Interobserver variability can be decreased to non-significant levels by a common training program. Thus, these indices can be widely applied to the study of arterial circulation in these organs.

Female↗

Aberrant dipeptidyl peptidase IV (DPP IV/CD26) expression in human hepatocellular carcinoma.

BACKGROUND/AIMS: Diagnosis of small nodular lesions in the liver is often difficult because polarization of hepatocytes under pathological conditions is not as easily determined as for glandular or squamous epithelia. The aim of the present study was to investigate whether the bile canalicular enzyme dipeptidyl peptidase IV (DPP IV) would be useful to assess the pattern of hepatocellular surface polarity in liver sections. METHODS: Expression of DPP IV activity was determined by enzymatic cytochemistry and image cytometry in 25 human hepatocellular carcinomas and five cirrhotic livers removed at transplantation. Samples from the central and/or peripheral portion of neoplastic nodules and from surrounding tissue were analyzed in each case. Control specimens were obtained from normal liver of seven patients who underwent surgery for non-neoplastic conditions. RESULTS: In normal liver, DPP IV activity was confined to the bile canalicular plasma membrane with a zone 3 predominance in the hepatic acinus. This was also the case in the majority of pathological non-neoplastic livers, but the cell distribution pattern of DPP IV was altered in all hepatocellular carcinomas: 2/25 cases were completely devoid of DPP IV activity and in the remaining 23 DPP IV expressing hepatocellular carcinomas, three different patterns were observed that deviated distinctly from the typical canalicular pattern: (i) canaliculi were distorted and convoluted and contained an abnormally high DPP IV activity; (ii) canalicular activity was lost and enzymatic activity was restricted to isolated spots; (iii) pseudoacinar structures of hepatocytes with both basolateral and apical DPP IV expression appeared. CONCLUSIONS: It is concluded that DPP IV is a useful bile canalicular enzyme to assess the functional polarization of hepatocytes and that aberrant DPP IV expression occurs in human hepatocellular carcinoma.

Bile Canaliculi↗

Intra- and extrahepatic arterial resistances in chronic hepatitis and liver cirrhosis.

Thirty patients with chronic hepatitis (CH), 84 with liver cirrhosis (LC) and 42 controls, underwent noninvasive measurement of hepatic artery resistance index (RI) by means of Doppler ultrasound (US), at the porta hepatis and in the intrahepatic branches, in order to investigate possible changes related to: (a) the liver disease; (b) the site of measurement; and (c) ageing. The intrahepatic RI differed among LC, CH and controls (0.731, 0.690 and 0.643, p < 0.05), whereas the RI at the porta hepatis did not (0.754, 0.748 and 0.729, respectively). Intrahepatic RI correlated with age in LC (r = 0.51, p < 0.0001) and in controls (r = 0.49, p < 0.001). In LC, it correlated also with the presence and size of esophageal varices (r = 0.32, p < 0.05). In conclusion, an increase of hepatic artery RI in chronic liver diseases can be demonstrated when assessed in the intraparenchymal branches. The increase of hepatic artery RI with ageing should be considered in future studies.

Adult↗