PubMed Health⌕ Search

Biomedical subjects

M Pozzi

Publications and source records attributed to M Pozzi.

At least 19 recordsLinked to original sources

The pulmonary involvement in portal hypertension: portopulmonary hypertension and hepatopulmonary syndrome.

Pulmonary abnormalities are common in patients with advanced chronic liver disease. Two distinct syndromes strictly related to the presence of portal hypertension, but clearly different from a pathophysiologic point of view, have been identified. Portopulmonary hypertension, characterized by an increased pulmonary arterial pressure, is due to a progressive arteriolar vasoconstriction induced by excess local production of vasoconstrictor substances. Hepatopulmonary syndrome results from intrapulmonary microvascular dilation caused by an inadequate synthesis or metabolism of putative pulmonary vasoactive substances leading to a functional vasodilation of the pulmonary vasculature, ultimately leading to hypoxemia. Controversies on pathogenesis imply different tentative therapeutic approaches for the medical management of these conditions. The development of portopulmonary hypertension or the hepatopulmonary syndrome has important clinical and prognostic implications facing the impact of new therapeutic strategies for the management of the main complications of advanced liver diseases on cardiopulmonary function.

Animals↗

Cardiovascular abnormalities in special conditions of advanced cirrhosis. The circulatory adaptative changes to specific therapeutic procedures for the management of refractory ascites.

Advanced liver disease is characterized by decreased arterial blood pressure and peripheral vascular resistances, increased cardiac output and heart rate in the setting of a hyperdynamic circulatory pattern favoured by total blood volume expansion, circulatory overload and overactivity of the endogenous vasoactive systems. Reduced heart responses to stressful conditions such as changes in loading conditions of the heart in presence of further deterioration of liver function such as refractory ascites, hepatorenal syndrome, spontaneous bacterial peritonitis and bleeding esophageal varices have been recently identified and the knowledge of the cirrhotic cardiomyopathy syndrome has gained the dignity of a new clinical entity. Facing the availability of therapeutic interventions (paracentesis, transjugular intrahepatic portosystemic shunt, peritoneovenous shunt, orthotopic liver transplantation) currently employed to manage the life-threatening complications of the most advanced phases of cirrhotic disease, the knowledge of their impact on cardiovascular function is of paramount relevance.

Adaptation, Physiological↗

Imaging work-up for peritoneal access care and peritoneal dialysis complications.

Peritoneal dialysis (PD) represents a treatment opportunity for patients with end-stage renal failure, but it has particular complications that sometimes force cessation of this procedure (1- 9). These complications are due to the presence of the peritoneal catheter and of dialysis solution within the peritoneal cavity. Infections are the most common complications of PD, followed by mechanical complications. Diagnostic imaging of the complications of PD is important because such an evaluation can aid in the diagnosis and in the decision making process about the treatment. In this review we present the main radiologic investigations employed: plain radiograph, US, peritoneography, computed tomography peritoneography, magnetic resonance peritoneography, peritoneal scintigraphy. To diagnose catheter-related problems plain radiograph, ultrasonography and peritoneography can be useful. US is useful in diagnosing and following-up exit-site and tunnel infections. Peritoneography and CT-peritoneography, alone or in combination, can be recommended as gold standard investigation to assess mechanical peritoneal dialysis complications, such as catheter malfunction, leaks, hernias and sclerosing peritonitis. Newer methods, such as MR peritoneography or scintigraphy could be useful in selected patients, on center-based experience. An appropriate use of radiology may significantly improve technique survival, morbidity and mortality of patients treated with PD.

Abdomen↗

Nipple sparing mastectomy with immediate breast reconstruction: a short term analysis of our experience.

Breast cancer surgery has greatly changed over the past decades; nowadays skin-sparing mastectomy (SSM) and immediate reconstruction is considered a valid oncological option to achieve good aesthetic results. The success of SSM led to several studies aimed to investigate NAC involvement whose removal increases the patient's sense of mutilation. In this study the Authors investigate the incidence of recurrences in nipple sparing mastectomy (NSM) comparing it with the other techniques to assess the actual risk of tumor involvement of the NAC; besides, they analyse the patients' satisfaction and the NSM impact on quality of life through the utilization of a questionnaire. Clinical complications, aesthetic as well as oncological and psychological results have been analysed. They conclude that in selected cases NSM can be performed without additional risks because the incidence of recurrence after NSM is similar to that of radical mastectomy. Moreover, the aesthetic and psychological outcome are considered positive by the patients.

Adult↗

Pathophysiology of portal hypertension in HCV-related cirrhosis. Putative role of assessment of portal pressure gradient in Peginterferon-treated patients.

Chronic HCV infection is the leading aetiologic factor for cirrhosis, end-stage liver disease, hepatocellular carcinoma and liver transplantation worldwide. Pegylation of alfa interferons has improved the management of this disease. Interferon treatment has antifibrotic and immunomodulatory activities. Recent evidence supports the contention that Hepatitis C virus-related cirrhosis of the liver should no more be considered an irreversible disease; fibrosis is a potentially reversible process. Fibrosis and even cirrhosis reversal have been previously demonstrated either in experimental or clinical studies of other liver diseases. Development of portal hypertension is the main drive to the complications of advanced liver diseases: prognosis worsens significantly when portal hypertension becomes clinically significant. It is thus conceivable that within therapeutic trials involving patients with advanced fibrosis of the liver, measurement of the hepatic venous pressure gradient, the gold standard in the clinical assessment of portal hypertension and its management, could provide information on the portal pressure-lowering effects of interferon treatment affecting the fibrosis score. This can be accomplished by either sustained virological response either by fibrosis reduction achieved by chronic low-dose Peginterferon administration. If the introduction of drug therapy with non-selective beta blockers in the treatment of portal hypertension represents a milestone in the treatment of patients with cirrhosis and high-degree portal hypertension, the next step must then be prophylactic reversal of initial portal hypertension prompted by either HCV eradication and pharmacological inhibition of fibrosis progression by long-term Peginterferon before higher degrees of portal hypertension ensue.

Antiviral Agents↗

Interferon-induced depression: prevalence and management.

BACKGROUND: Interferon-induced depression ranges from 0 to 50%. Interferon schedule and a history of psychiatric illnesses are not enough to predict who will develop symptoms and who will not. AIMS: To assess the prevalence of depression during interferon therapy; to test whether Minnesota Multiphasic Personality Inventory is useful in clinical practice for the early identification of patients at risk of depression; whether and how the depression can be cured. PATIENTS: One hundred and eighty-five patients treated with interferon and ribavirin for chronic hepatitis C. METHODS: Before therapy, all patients underwent a Minnesota Multiphasic Personality Inventory and a clinical examination, specifically for the identification of depressive symptoms. RESULTS: Thirty-one patients developed a psychiatric disorder, 11 of them requiring treatment with anti-depressant drugs. Among the 18 patients with Minnesota Multiphasic Personality Inventory positive tests, 16 developed a psychiatric disorder, 8 of them a severe disorder (sensitivity of 0.58; 0.73 for severe disorders). Among the 154 who did not develop psychiatric side effects, 152 had a negative Minnesota Multiphasic Personality Inventory (specificity: 0.99). Severe psychiatric disorders were successfully treated with anti-depressant drugs. CONCLUSIONS: Psychiatric side effects are easy to see during interferon therapy. A psychiatric evaluation should be considered on all patients before treatment. If depression develops, it should be treated aggressively, and selective serotonin re-uptake inhibitors are the anti-depressants of choice.

Adult↗

[Diastolic dysfunction in liver cirrhosis].

The presence of a hyperdynamic circulation in cirrhotic liver is currently a well established concept. The first studies of cardiac function in patients with cirrhosis suggested the existence of an alcoholic cardiomyopathy. More recently, altered left ventricular response to physiological and/or pharmacological stimuli in patients with post-viral liver cirrhosis has been established, and clinically insignificant diastolic cardiac function has also been observed. Neurohumoral hyperactivity and hyperdynamic circulation, which are associated with chronic exposure to the cardiodepressant substances present in advanced liver disease, play a decisive role in the genesis of this process. The lack of relaxation of the left ventricle and alteration in the pattern of transmitral flow, both of which are characteristics of this clinical entity, are easily detected by echocardiography. The growing evidence of diastolic dysfunction in liver cirrhosis, particularly in decompensated cirrhosis, suggests the clinical importance of the problem, thus introducing the concept of "cirrhotic cardiomyopathy". Greater insight into this phenomenon could help to decrease cardiovascular risk, especially during maneuvers commonly used in the treatment of the complications of liver cirrhosis, such as paracentesis, transjugular intrahepatic portosystemic shunt stent implantation, and liver transplantation.

Compliance↗

Time-course of diastolic dysfunction in different stages of chronic HCV related liver diseases.

AIM: A hyperdynamic circulatory pattern in advanced liver disease is known since a long time. The first studies evaluating cardiac function in cirrhosis were performed in patients with alcoholic liver disease and thus this condition was attributed to the toxic effects of ethanol. A reduced performance of the left ventricle after physical and pharmacological strains along with an altered diastolic function has been demonstrated also in postviral cirrhosis. Many factors are involved in advanced cirrhosis whereas little is known in the earlier stages of disease. METHODS: To this aim we have investigated patients with different stages of hepatitis C virus (HCV)-related liver disease to detect the time-course of diastolic dysfunction. An impaired relaxation and increased thickness of left ventricular walls along with an altered pattern of transmitral flow can be easily detected by means of echocardiography. RESULTS: In chronic hepatitis diastolic function is preserved but increased thickness of left ventricle parietal walls can be detected in patients with fibrosis on liver biopsy. The typical pattern of diastolic dysfunction is observed in Child A cirrhotic patients and in Child C ascitic patients but thickness of parietal walls is more relevant in the former group. Chronic aldosterone blockade could exert favourable effects in heart remodeling suggesting a potential role of these drugs in cirrhotic cardiomyopathy. CONCLUSIONS: The presence of increased thickness of left ventricle parietal walls in chronic hepatitis C in the precirrhotic stage point to a putative role of HCV in this heart structural abnormality that can become a co-factor in the more advanced stages of cirrhosis when portal hypertension and its deleterious effects on systemic hemodynamics, cardiac function and structure become manifest.

Aged↗

The impact of cardiopulmonary bypass on selenium status, thyroid function, and oxidative defense in children.

Selenium has important functions for oxidative defense and thyroid hormone metabolism. Selenium-dependent enzymes include 5'-iodothyronine deiodinase and glutathione peroxidase (GPX). The objective of this study was to investigate the relationship between plasma selenium, GPX activity, and thyroid hormone status in pediatric cardiac surgical patients. Plasma concentrations of selenium, free triiodothyronine (fT3), free thyroxin (fT4), and c-reactive protein as well as plasma activity of GPX were prospectively evaluated at anesthetic induction and 48 hours postoperatively in 59 children requiring cardiopulmonary bypass (CPB). GPX was measured at additional time points at 6, 12, and 24 hours postoperatively. There was a significant reduction in the plasma selenium concentration after cardiopulmonary bypass with obtained median measurements of 0.61 micromol/L (induction) and 0.51 micromol/L (48 hours postoperatively). The fT3/fT4 ratio decreased significantly from 0.28 at anesthetic induction to 0.22 at 48 hours postoperatively. There were no significant changes of GPX activity. 48 hours fT3 concentration, fT3/fT4 ratio, and selenium concentration were significantly negatively correlated with the time spent in intensive care. The concentration of plasma selenium in children undergoing cardiopulmonary bypass significantly decreases, resulting in diminished deiodinase activity, and a subsequent reduction in the conversion of T4 to T3.

Adolescent↗

The Aristotle score: a complexity-adjusted method to evaluate surgical results.

OBJECTIVES: Quality control is difficult to achieve in Congenital Heart Surgery (CHS) because of the diversity of the procedures. It is particularly needed, considering the potential adverse outcomes associated with complex cases. The aim of this project was to develop a new method based on the complexity of the procedures. METHODS: The Aristotle project, involving a panel of expert surgeons, started in 1999 and included 50 pediatric surgeons from 23 countries, representing the EACTS, STS, ECHSA and CHSS. The complexity was based on the procedures as defined by the STS/EACTS International Nomenclature and was undertaken in two steps: the first step was establishing the Basic Score, which adjusts only the complexity of the procedures. It is based on three factors: the potential for mortality, the potential for morbidity and the anticipated technical difficulty. A questionnaire was completed by the 50 centers. The second step was the development of the Comprehensive Aristotle Score, which further adjusts the complexity according to the specific patient characteristics. It includes two categories of complexity factors, the procedure dependent and independent factors. After considering the relationship between complexity and performance, the Aristotle Committee is proposing that: Performance = Complexity x Outcome. RESULTS: The Aristotle score, allows precise scoring of the complexity for 145 CHS procedures. One interesting notion coming out of this study is that complexity is a constant value for a given patient regardless of the center where he is operated. The Aristotle complexity score was further applied to 26 centers reporting to the EACTS congenital database. A new display of centers is presented based on the comparison of hospital survival to complexity and to our proposed definition of performance. CONCLUSION: A complexity-adjusted method named the Aristotle Score, based on the complexity of the surgical procedures has been developed by an international group of experts. The Aristotle score, electronically available, was introduced in the EACTS and STS databases. A validation process evaluating its predictive value is being developed.

Cardiac Surgical Procedures↗

Intracerebral self-administration of the cannabinoid receptor agonist CP 55,940 in the rat: interaction with the opioid system.

The effect of CP 55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclo-hesanol], heroin and etonitazene on intracerebroventricular (i.c.v.) self-administration in a free-choice procedure was evaluated in rats. Animals were trained in 1-h daily sessions with a continuous reinforcement schedule to press two active levers to obtain the vehicle of each drug. Then, when a stable baseline was reached, each drug could be self-administered by pressing the lever found to be less preferred during training, while the vehicle came from the other. The number of bar pressings associated with the delivery of increasing unit doses of CP 55,940 (0.1, 0.2, 0.4, 0.8, 1.6 microg/2 microl/infusion), heroin (0.125, 0.25, 0.5, 1, 2 microg/2 microl/infusion) or etonitazene (0.1--0.2--0.5--1 microg/ 2 microl/infusion) and with the delivery of the corresponding vehicle was fitted by symmetrical parabolas. The mean drug intake was linearly related to the log of self-administered drugs. Pretreatment with SR141716A [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichloro-phenyl)-4-methylpyrazole-3-carboxamide] (0.5 mg/kg) or naloxone HCl (2 mg/kg/i.p.) 15 min before each daily session reduced the self-administration of both CP 55,940 and heroin. The combination of CP 55,940 with heroin or etonitazene reduced the number of drug-associated lever pressings compared to that obtained with the maximal reinforcing unit dose of each drug alone. These findings suggest there may be a strong interaction between opioids and the cannabinoid system.

Analgesics↗

Norwood-type operation with adjustable systemic-pulmonary shunt using hemostatic clip.

The postoperative course of a patient with hypoplastic left heart syndrome after a first-stage Norwood operation is governed to a large extent by the balance between the systemic and pulmonary circulations. Here we describe a simple and convenient technique for establishing an optimally sized systemic-pulmonary shunt by the application of a hemostatic clip. The method has been used in 6 patients.

Aorta, Thoracic↗

Conditioned place preference induced by the cannabinoid agonist CP 55,940: interaction with the opioid system.

Cannabinoids appear atypical as drugs of abuse since controversial data exist concerning the ability to lower the thresholds for electrical self-stimulation (Stark and Dews, 1980; Gardner et al., 1988; Gardner, 1992) and to support self-administration (Martellotta et al., 1998; Tanda et al., 2000) or conditioned place preference in animals (Lepore et al., 1995; Parker and Gillies, 1995; McGregor et al., 1996; Sañudo-Peña et al., 1997; Chaperon et al., 1998; Hutcheson et al., 1998; Mallet and Beninger, 1998; Cheer et al., 2000; Valjent and Maldonado, 2000). Opioids and cannabinoids share some pharmacological properties (Manzanares et al., 1999). The most interactions were found in antinociception (Welch and Stevens, 1992; Smith et al., 1994) and, to a lesser extent, in drug reinforcement (Chen et al., 1990; Vela et al., 1995; Tanda et al., 1997). In the present study we asked whether: (1) a potent synthetic cannabinoid receptor agonist, [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptil)-phenyl]-trans-4-(3-hydroxy propyl) cyclohexanol] (CP 55,940) (from 10 to 40 microg/kg), which binds to the brain cannabinoid receptors with high affinity (Herkenham et al., 1991), would induce conditioned place preference, in comparison with heroin (from 0.1 to 5 mg/kg); (2) what type of receptor was involved; (3) what kind of interaction there was between the two drugs, when given in combination, on reward. CP 55,940 elicited a conditioned place preference only at a dose of 20 microg/kg similar in intensity to that of heroin (2 mg/kg). The reinforcing properties of the cannabinoid agonist were fully antagonised by pretreatment with the brain cannabinoid receptor-1 (CB(1)) antagonist, [N-piperidino-5-(4-chlorophenyl) 1-(2,4-dichloro-phenyl)-4-methyl pyrazole-3-carboxamide hydrochloride] (SR 141716A) and naloxone. The combination of CP 55,940 and heroin, at the reinforcing doses, led to a reward which did not show any additive effect. Taken together these findings are important for understanding how the cannabinoids produce reward and the interconnection of the opioid and cannabinoid system in the motivation.

Analgesics↗

Post-cardiotomy mechanical circulatory support using a conventional bypass circuit in children.

OBJECTIVE: Mechanical circulatory support (MCS) is increasingly used after cardiotomy in children when conventional medical treatment fails. Poor overall survival and long-term outcome have been reported. We report our experience of post-cardiotomy MCS using a conventional bypass circuit. METHODS: Over a 4 year and 6 month period 10 patients, with a median age of 16 days (range 5 days to 16 years) required MCS. Eight patients required support for failure to wean from cardiopulmonary bypass during primary correction. Two patients required support for cardiac arrest or poor cardiac output in the postoperative period. RESULTS: The median duration of support was 43 h (range 26-146 h). Seven hospital survivors were alive and well at median follow-up of 18 months (range 4-36 months). One patient could not be weaned off support. Two more patients died after successful weaning from support. Complications in nine patients who could be weaned off support included renal failure (n=6), cerebrovascular events (n=3) and mediastinitis (n=2). CONCLUSIONS: Overall long-term survival (70%) and quality of recovery is usually good even though initial mortality and complication rates may be high. We think that post cardiotomy mechanical circulatory bypass using a conventional bypass circuit can offer a favourable outcome to selected patients.

Adolescent↗

Patterns of regional sympathetic nerve traffic in preascitic and ascitic cirrhosis.

Overactivity of the sympathetic nervous system and portal hypertension are key factors in the development of ascites in cirrhosis. The sympathoexcitation that characterizes the more advanced stages of liver diseases is less clearly defined in preascitic cirrhosis. We measured sympathetic nerve traffic to skeletal muscle (peroneal nerve) and to skin districts by microneurography in (1) 12 Child class A cirrhotic patients with clinically significant portal hypertension (portal pressure gradient > 10 mm Hg, 14.8 +/- 1.2 mm Hg, mean +/- SEM) but without actual or previous ascites, (2) 16 Child class C cirrhotic patients with tense ascites, and (3) 10 patients with mild congestive heart failure, a condition paradigmatic of a marked sympathetic activation. Muscle sympathetic nerve traffic was markedly increased in Child class C subjects as compared with controls (23.9 +/- 1.6 bursts/min, P <.01) and superimposable to that recorded in heart failure patients (52.9 +/- 4.7 vs. 60.3 +/- 2 bursts/min, P = not significant). Muscle sympathetic nerve traffic was also increased in Child class A subjects (41.6 +/- 2 bursts/min, P <.01 vs. controls) although to a lesser extent (P <.05 vs. Child class C patients). Skin sympathetic nerve traffic was within the normal range in all patients. Neurohormones were all markedly increased in Child class C subjects. Only norepinephrine was increased in Child class A patients. Our data show that sympathetic nerve traffic activation (1) is already detectable in Child class A cirrhosis when clinically significant portal hypertension is present but ascites never developed and (2) is not generalized because although muscle traffic is increased, skin traffic is within normal range. The role of drugs modulating sympathoactivation should be investigated in preascitic cirrhosis.

Aged↗

Outcome of liver disease in a large cohort of histologically proven chronic hepatitis C: influence of HCV genotype.

OBJECTIVE: To assess the influence of hepatitis C virus (HCV) genotypes on the clinical outcome of liver disease, we analysed 2,307 patients. RESULTS: The most frequently represented genotypes were 1b (40%) and 2 (28.1%). Patients with these genotypes had a median age higher than patients with other genotypes (P< 0.01). The overall survival of subjects with genotype 1b was poorer than the survival of patients with other genotypes (P< 0.01). Liver cirrhosis was found in 280 patients (12.1%), and type 1b was the most represented isolate among them (P< 0.01). Sixty-two patients (22%) developed hepatocellular carcinoma (HCC) during a follow-up of 1481.8 cumulative years (estimated crude incidence rate, 4.1 cases per 100 person-years for all cirrhotics; 5.9 cases for genotype 1a; 4.5 cases for genotype 1b; and 2.8 cases for genotypes non-1). Considering the whole population of 2,307 patients, only genotype 1b was associated significantly with both cirrhosis and the development of HCC. One hundred and nineteen cirrhotic patients underwent treatment with interferon in uncontrolled studies. Interferon therapy was associated with both better survival (P< 0.01) and a lower cumulative hazard for HCC (P< 0.01). CONCLUSIONS: Genotype 1b was associated with a poorer prognosis, probably because it leads to cirrhosis and consequently to HCC development. However, our data did not confirm genotype 1b as an independent risk factor for HCC in liver cirrhosis, which plays a major role in carcinogenesis. Interferon should be considered as a useful strategy in cirrhosis for improvement of survival and reduction of HCC risk.

Adolescent↗

CP 55,940 protects against ischemia-induced electroencephalographic flattening and hyperlocomotion in Mongolian gerbils.

The effect of CP 55,940, on electroencephalographic (EEG) spectral power decrease and hyperlocomotion induced by transient global ischemia in gerbils, was investigated. Animals were treated with CP 55,940 (4 mg/kg intraperitoneal (i.p.)) 5 min after bilateral carotid occlusion or SR 141716A (3 mg/kg i.p.) 5 min before or with both. Mean total and relative spectral power was evaluated for 1 h before (basal) and 1 and 24 h, 3 and 7 days after ischemia. Spontaneous locomotor activity was evaluated at the same times. CP 55,940 antagonized the reduction in mean total spectral power and the hyperlocomotion induced by ischemia, in comparison with vehicle group, starting from 24 h and lasting 7 days (P<0.001). Pretreatment with SR 141716A completely blocked the neuroprotective effect of CP 55,940. These findings suggest a potential therapeutic role of cannabinoids in cerebral ischemia.

Analgesics↗