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Biomedical subjects

M Rizzetto

Publications and source records attributed to M Rizzetto.

At least 37 records · Page 2Linked to original sources
PubMed2005

Hepatic involvement in larva migrans of Toxocara canis: report of a case with pathological and radiological findings.

Patients with the clinical syndrome of visceral larva migrans as a result of Toxocara species, have typical lesions in the liver consisting of granulomas that contain numerous eosinophils and often Charcot-Leyden crystals. This syndrome is rarely taken into account in patients with cholestatic syndrome, especially when hypereosinophilic reaction is absent. We report the case of a 47-year-old immunocompetent woman who presented with abdominal pain, in whom multiple focal liver lesions were discovered. She had come in contact with dogs. Diagnosis of toxocariasi was done. A good clinical response has been obtained by treating with thiabendazole. We present the findings of various imaging studies of the patient. This report shows that visceral larva migrans may be the cause of a chronic liver disease and should be suspected also in patients without fever and hypereosinophilia with cryptogenic cholestatic and focal liver lesions.

Animals↗
PubMed2005

Lamivudine therapy in chronic delta hepatitis: a multicentre randomized-controlled pilot study.

BACKGROUND: Delta virus (HDV)-related chronic hepatitis is difficult to treat. AIMS: To evaluate the efficacy of lamivudine 100 mg daily on serum HDV-RNA, hepatitis D virus antibodies and alanine aminotransferase levels, liver histology, and on hepatitis B surface antigen seroconversion. METHODS: Thirty-one hepatitis B surface antigen-positive, HDV-RNA-positive patients with ALT > or = 1.5 upper normal level and compensated liver disease were randomized (1:2 ratio) to placebo (group A, n = 11) or lamivudine (group B, n = 20) for 52 weeks; thereafter, all patients were given lamivudine for 52 weeks and followed up for 16 weeks. RESULTS: Twenty-five patients (81%) completed the study. No patient was HDV-RNA-negative at week 52; three patients (11%) were negative at week 104. Two of them remained HDV-RNA-negative at week 120, and one lost the hepatitis B surface antigen without seroconversion. Paired pre-treatment and week 104 liver biopsies were available from 19 patients: of which three of seven (43%) from group A and two of 12 patients (17%) from group B had a > or =2 point decrease in the Ishak necroinflammatory score. CONCLUSION: A sustained complete response was achieved in 8% of hepatitis D virus-infected patients treated with lamivudine and a partial histological response in 26% of them. Hepatitis D virus viraemia was unaffected, even in patients when hepatitis B virus replication was lowered by lamivudine therapy.

Adult↗
PubMed2005

Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms.

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) has been associated with the metabolic syndrome. However, it is not clear whether insulin resistance is an independent feature of NAFLD, and it remains to be determined which of the in vivo actions of insulin are impaired in this condition. METHODS: We performed a two-step (1.5 and 6 pmol min(-1) kg(-1)) euglycaemic insulin clamp coupled with tracer infusion ([6,6-2H2]glucose and [2H5]glycerol) and indirect calorimetry in 12 non-obese, normolipidaemic, normotensive, non-diabetic patients with biopsy-proven NAFLD and six control subjects. RESULTS: In NAFLD patients, endogenous glucose production (basal and during the clamp) was normal; however, peripheral glucose disposal was markedly decreased (by 30% and 45% at the low and high insulin doses, respectively, p<0.0001) at higher plasma insulin levels (p=0.05), due to impaired glucose oxidation (p=0.003) and glycogen synthesis (p<0.001). Compared with control subjects, glycerol appearance and lipid oxidation were significantly increased in NAFLD patients in the basal state, and were suppressed by insulin to a lesser extent (p<0.05-0.001). The lag phase of the in vitro copper-catalysed peroxidation of LDL particles was significantly shorter in the patients than in the control subjects (48+/-12 vs 63+/-13 min, p<0.04). Lipid oxidation was significantly related to endogenous glucose production, glucose disposal, the degree of hepatic steatosis, and LDL oxidisability. CONCLUSIONS/INTERPRETATION: Insulin resistance appears to be an intrinsic defect in NAFLD, with the metabolic pattern observed indicating that adipose tissue is an important site.

3-Hydroxybutyric Acid↗
PubMed2005

Evidence of a dynamic aldosterone-independent distal tubular control of renal sodium excretion in compensated liver cirrhosis.

BACKGROUND AND AIM: In preascitic cirrhosis increased sodium retention occurs in kidney distal tubule in spite of normal aldosterone plasma levels. No clearance technique can dissect the respective contribution to sodium retention exerted by Henle's loop, distal convoluted tubule and collecting duct, so we evaluated proximal and distal tubular sodium handling in preascites during two manoeuvres that temporarily increase aldosterone secretion. METHODS: Ten patients with compensated cirrhosis and nine controls were studied in recumbency, during standing and after dopamine receptor blockade with metoclopramide through: 4 h renal clearances of sodium, potassium, lithium and creatinine; plasma levels of active renin and aldosterone. RESULTS: Whilst comparable in recumbency, aldosterone levels significantly rose during standing and after metoclopramide in both groups. In patients, dopaminergic blockade caused a fall of distal sodium delivery (P < 0.01) but urinary sodium excretion was unchanged because the reabsorbed fraction of distal sodium delivery also fell (P < 0.03). Cirrhotic patients showed the same findings in the passage from recumbency to standing. CONCLUSIONS: In preascitic cirrhosis, the distal tubular segments of the nephron are able to cope with decreases in tubular flow by reducing reabsorption at an aldosterone-independent site (possibly the loop of Henle).

Adult↗
PubMed2005

Treatment of hepatitis D.

Delta virus related chronic hepatitis is difficult to treat. The response to alpha-interferon (IFN), which still represents the only therapy for chronic hepatitis D, varies widely and occurs at different times from the beginning of treatment. The rate of response is proportional to the dose of IFN, with 9 million units (MU) three times a week being more effective than 3 MU thrice weekly. Sustained responses are unusual and are accompanied by the clearance of serum hepatitis B virus surface antigen (HBsAg), seroconversion to anti-HBs and improvement of liver histology. Although disease of a short-standing may respond better to therapy, clear predictors of response are still unidentified. Besides IFN, other therapeutic approaches such as immunosuppressive drugs, acyclovir, ribavirin and thymosin, have been unhelpful. Available evidence does not support the use of deoxynucleotide analogues. Famciclovir has no effect on disease activity and hepatitis D virus (HDV)-RNA levels. Twelve- or 24-month lamivudine treatment does not significantly affect biochemical, virological or histological parameters. Pegylated-IFN could represent a reasonable therapeutic option in the long-term treatment required for chronic hepatitis D. Antisense oligonucleotides and prenylation inhibitors hold promise as therapeutic agents of the future. Liver transplantation provides a valid option for end-stage HDV liver disease; the risk of re-infection is lower for HDV than for HBV under long-term administration of hyperimmune serum against HBsAg. Molecularly tailored drugs capable of interfering with crucial viral replicative processes of HDV appear to be the best prospect in the treatment of hepatitis D.

Clinical Trials as Topic↗
PubMed2005

Natural history of hepatitis C virus infection: from chronic hepatitis to cirrhosis, to hepatocellular carcinoma.

Hepatitis C is a heterogeneous disease and is responsible for considerable mortality and morbidity. The hepatitis C virus (HCV) infects nearly 170 million people world-wide. More than 80% of infected individuals develop chronic infection; the remaining 10-20% develop spontaneous clearance with natural immunity. Acute hepatitis is icteric in only 20% of patients and is rarely severe. The majority of patients who develop chronic HCV infection are asymptomatic; but 60-80% develop chronic hepatitis as indicated by elevated alanine aminotransferase (ALT), around 30% maintain persistently normal ALT levels despite having detectable HCV-RNA in serum. One-third of chronically infected patients develop progressive liver injury, fibrosis and cirrhosis over a period of 20-30 years. The relationship between virus load, HCV genotype, quasi-species variability and progression of liver disease is controversial. Acquired infection after age 40, male sex, excessive alcohol-consumption, hepatitis B virus (HBV) or HIV co-infection, steatosis, and immunosuppressed state have been identified as co-factors associated with progression of fibrosis and development of cirrhosis. In patients with cirrhosis, the incidence of hepatocellular carcinoma is 2-5% per year. At present, HCV-related end-stage cirrhosis is the first cause of liver transplantation.

AIDS-Related Opportunistic Infections↗
PubMed2005

Autoimmune manifestations during interferon therapy in patients with chronic hepatitis C: the hepatologist's view.

In face of numerous benefits induced by therapy based on interferon (IFN) associated with ribavirin for the treatment of chronic hepatitis C, there is an increasing concern regarding its tolerance, which can, in some cases, reduce the quality of life as well as compliance of patients. Among the less common side effects, there are the autoimmune ones which can be globally divided into appearance or increase in titres of auto-antibodies and/or manifestation of overt autoimmune pathologies. Whereas the former may concern more than 50% of treated subjects, the latter is reported in only 1-2% of patients under therapy. Thyroid dysfunction represents the well-studied autoimmune disorder. The presence of pre-existing anti-thyroid antibodies and being of female sex, constitute relevant risk factors for the development of a disease involving this gland. Often the treatment of thyropathy must be continuous in spite of IFN discontinuation because the disturbance usually does not abate with stopping antiviral therapy. Some observations have pointed out to the fact that IFN can lead to the development of insulin-dependent diabetes mellitus. Sometimes, during, as well as after IFN treatment, the appearance of anti-islet cell antibodies has been shown, but its interrelationship with the development of disease is uncertain. While being treated with IFN for chronic hepatitis C, the finding of non-organ specific antibodies at baseline can increase the likelihood of the development of autoimmune hepatitis. However, their presence does not constitute an absolute contraindication to the treatment, except in case of high titre. Other disorders, such as a lupus erythematosus-like syndrome, haemolytic anaemia, and immune-mediated thrombocytopenia have been reported. In conclusion, although the presence of auto-antibodies is considered to be an epiphenomenon without pathogenic significance in most patients suffering from chronic hepatitis C, it poses a problem when they need to be treated with IFN. This antiviral drug can induce or exacerbate a multitude of autoimmune-related disorders, however, clinically overt immune-mediated diseases are rare and affect a subset of subjects who have an underlying autoimmune diathesis.

Antiviral Agents↗
PubMed2005

[Intestinal metaplasia, dysplasia, gastric cancer and Helicobacter pylori: epidemiological observations].

Gastric cancer (GC) is the world's second leading cause of cancer-related mortality, and carries a bad prognosis. In 1994, Helicobacter pylori (H. pylori) has been classified by the International Agency for Research on Cancer as a group I carcinogen. There are increasing indications that this infection is associated with both the initiation and progress of gastric carcinoma and lymphoma. Evidence supporting a causal association has been demonstrated by epidemiological data and in experimental animal models. Despite this, there is still lack of final conclusion regarding the association between the infection and the malignancy due both to marked geographic variations and heterogeneity in study designs. Given the high rate of morbidity and mortality associated with GC, any means of reducing the occurrence of the disease or increase its early detection is most desirable. In this paper, the epidemiological aspects on the evidence of a causal relationship between H. pylori and GC are discussed. Prospective cohort studies and interventional trials focused on the effects of H. pylori eradication on lesions predisposing to GC should be performed in order to provide further data.

Adenocarcinoma↗
PubMed2005

Association between Crohn's disease and Conn's syndrome. A report of two cases.

The natural history of Crohn's disease (CD) is characterised by periods of remission followed by phases of flares. Persistent or intractable diarrhoea may be associated with ileal disease or arise following ileal resection, resulting in potassium depletion. Medical therapy with steroids presents troublesome side-effects (e.g. hypertension). Conn's syndrome, caused by unilateral aldosterone-producing adenoma, is characterised by clinical features including hypokalaemia and hypertension. Thus, CD and Conn's syndrome may have an overlap of manifestations, and up to now, the simultaneous occurrence of these conditions has not been described. We report here 2 cases of association between CD and Conn's syndrome.

Adrenalectomy↗
PubMed2005

[Screening for hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is common throughout the world. The incidence of HCC is higher in cirrhotic patients and, among these patients, the incidence rate is 3% in Europe. The overall survival rate of HCC ranges between 20 and 30 months, and is influenced by the local stage of the neoplasm and by the liver function. The literature reports several serological, urinary and radiological markers used for the early detection of HCC. Currently, it is highly recommended to periodically screen cirrhotic patients and hepatitis B virus carriers older than 35 by serum alpha-fetoprotein (AFP) and liver ultrasound (US) every 6 months. The concomitant determination of des-g-carboxy prothrombin and AFP allows a 23% increase in sensibility of the diagnosis for HCC avoiding the need for invasive diagnostic procedures.

Biomarkers↗
PubMed2005

How accurate is the culture of Helicobacter pylori in a clinical setting? An appraisal.

AIM: The trend towards increasing prevalence of Helicobacter pylori (H. pylori) antibiotic resistance may jeopardize the efficacy of most regimens. Culture of the bacterium, the useful method able to address therapy, is influenced by various factors. Thus, validation of the procedure is fundamental. Most studies have been carried out in microbiological settings, while only few have been conducted in clinical frames. We evaluated the accuracy of culture for detection of H. pylori in a clinical dedicated laboratory. METHODS: Forty-six patients (28 females, 18 males, mean age 56+/-4.7 years) were included. Thirty experienced failure to H. pylori eradication after at least 3 courses of treatment. The control group included 16 subjects suffering from gastroesophageal reflux disease and negativity for H. pylori infection. Diagnostic strategy was based on histology, culture testing, serology and 13C-urea breath test. A patient was considered infected if 2 tests were positive. A commercial culture medium in microaerophilic atmosphere was utilized. RESULTS: Out of 30 positive specimens, culture correctly identified 29. In 1 case, no growth of micro-organisms occurred. In the control group, bacterial culture accurately identified all negative samples. One of them indicated growth but neither aspect nor confirmation tests identified H. pylori. Sensitivity was 96.7%, specificity 100%, and accuracy 97.8%. Positive and negative predictive values were 100% and 94.1%, respectively. CONCLUSIONS: Culture of H. pylori is a feasible method and provides a good level of diagnostic accuracy even in a clinical setting by following international guidelines combined with training of specialized personnel.

Breath Tests↗
PubMed2004

Four years of treatment with lamivudine: clinical and virological evaluations in HBe antigen-negative chronic hepatitis B.

AIM: To evaluate the clinical and virological impact of the prolonged use of lamivudine in 94 patients with HBe antigen-negative chronic hepatitis B. METHODS: Initial virological and biochemical responses were obtained in 84 (89%) and in 83 (88%) patients respectively. RESULTS: The virological response peaked within the first 12 months, but diminished to 39% at 48 months because of drug resistance. Overall a virological breakthrough developed in 44 patients (52.4%). After virological breakthrough, the actuarial probability of maintaining biochemical remission diminished to 15% at 24 months and 0% at 29 months. There was no response in 10.6%. Polymerase gene mutations were observed in 82.5% of virological breakthroughs but also in 75% of the non-responders. Overall 7.4% of patients developed a hepatocellular carcinoma. CONCLUSION: Almost 90% of patients responded initially to lamivudine but the emergence of drug resistance progressively reduced the rate of virological remission to 39% at the fourth year of therapy. YMDD mutants explained the 75% of lamivudine resistances and were also selected very early in non-responders. Although the biochemical response is invariably lost within 29 months of the YMDD mutant's duration, the clinical outcome was benign despite severe postvirological breakthrough hepatitic flares in about 12% of cases.

Antiviral Agents↗
PubMed2004

The use of the anti-tumour necrosis factor monoclonal antibody--infliximab--to treat ulcerative colitis: implications and trends beyond the available data.

The monoclonal antibody to the tumour necrosis factor--infliximab--has recently been added to the list of off-label therapeutic means for ulcerative colitis. We conducted a descriptive analysis of the results from studies on the use of the drug published so far. A total of 187 patients qualified for analysis. They were divided into four main categories, including steroid-refractory and responsive adults and children. The median frequencies of an early and a sustained response were 77 and 44.5%. These data suggest that adult non-steroid-refractory, and paediatric patients may respond with the highest frequency. While it is obligatory to wait for the yield of the ongoing controlled trials before any conclusion on these indications is drawn, the data provide seminal ideas to further investigations, including the hypothesis to inaugurate with infliximab a top-down strategy for the treatment of inflammatory bowel disease.

Antibodies, Monoclonal↗
PubMed2004

Long-term efficacy of oral microemulsion cyclosporin for refractory ulcerative colitis.

AIM: The 60% bioavailable oral microemulsion formulation of cyclosporin (NEORAL ), has replaced the intravenous route to treat both organ transplant and immune-based disease. Its use for steroid-refractory ulcerative colitis (a recognized indication for intravenous cyclosporin) has been scanty. METHODS: Twenty-three consecutive patients (14 male/9 female, universal colitis 14/23) entered a 3-month course of NEORAL (initially dosed at 5 mg/kg/day) because of steroid-refractoriness (14 cases) and steroid-dependence (9 cases). Responders (at least showing a 50% reduction of a clinical activity score) were continued on azathioprine. The initial steroid dose was tapered on commencing NEORAL; patients requiring steroid resumption or increase in the follow-up were defined as relapsers. RESULTS: The target trough concentration of 200 ng/ml of whole blood was achieved without major titration in all but 1 patient. There were 7 non-responders (30%). Of the 16 responders (70%), 2 have not relapsed; the remaining 14 relapsed at the median time of 9.5 months (1.5-60) with 10 (71%) showing only 1 relapse. Five patients were colectomized 12 months after NEORAL (1.5-24), leaving 11 of the initial 23 (47%) with their colon. Of the 16, all but 1 had azathioprine; the median daily steroid needs fell from 32 to 5 mg. CONCLUSION: The rates of acute and chronic response of 70% and 47% achieved by NEORAL in this indication duplicate the figures achieved by the traditional schedules of cyclosporin administration.

Administration, Oral↗
PubMed2004

Gastro-oesophageal reflux disease and asthma: would be possible to improve therapy on the basis of what is now known?

Gastro-oesophageal reflux disease (GORD) is a chronic and relapsing clinical condition, associated or not to histopathologic alteration resulting from repeated contact of oesophageal mucosa with gastric content. This condition occurs with high prevalence in the general population and represents one of the most frequent reasons for health care-seeking addressed to primary care physician and gastroenterologists. A plethora of extra-oesophageal manifestations have been described in patients suffering from GORD and a causal relationship has been postulated by many investigators. A large cohort of studies has focused on the possible cause-effect interaction between GORD and asthma. However, despite the improvement in both asthma symptoms and medication requirements after anti-secretory therapy, no change in pulmonary function is evident. Furthermore, the pathogenetic mechanism, a vagally mediated reflex, microaspiration or increasing reactivity to the stimuli, is yet unclear. Since conflicting conclusions and the failure to find a causal relationship are generally due to the heterogeneity of the studies, further research is needed to clarify the role of GORD in asthma pathogenesis, or viceversa, and whether a medical or surgical anti-secretory treatment may be an approach to curing the asthma patients non-responders to the classical therapy.

Asthma↗
PubMed2004

Is hepcidin the bridge linking Helicobacter pylori and anemia of chronic infection? A research proposal.

Since the last decade, several studies have reported on the link between chronic Helicobacter pylori (H. pylori) or Helicobacter species (H. species) infection and a variety of extragastric manifestations, comprising iron-deficiency anemia. A crucial question concerns which possible pathogenic mechanism of H. pylori infection may be involved in chronic anemia. Recent findings support the hypothesis that in subjects with H. pylori-positive gastritis, concomitant changes in intragastric pH and ascorbic acid are present that might play a role in impairing alimentary iron absorption with consequent sideropenic anemia. It has also been speculated that H. pylori infected antrum could act as a sequestering focus for iron. The bacterium enhances gastric lactoferrin, which captures iron from transferrin. The iron thus bound to lactoferrin is in turn picked up by the bacterium, by means of its outer membrane receptors, for its own growth. These models, however, are not able to answer why iron-deficiency anemia does not develop in all infected subjects. Recently, a new anti-microbial liver-made peptide, namely hepcidin, has been characterised. The link between hepcidin induction, inflammation and anemia both in humans and in animal models supports its key role as mediator of anemia of inflammation. In the present paper, we highlight the data available on the association between H. pylori and iron-deficiency anemia and, we propose to evaluate a possible mechanism involving hepcidin in a bridging role linking the infection to the anemia.

Anemia, Iron-Deficiency↗
PubMed2004

The epidemiology of hepatitis C virus infection. An update for clinicians.

Since the advent of sensitive diagnostic blood tests for the detection of antibody to hepatitis C virus (HCV) in donors, there has been a large decline in the incidence of transfusion-related hepatitis. Globally, the infection has an estimated prevalence of 3%, with a prevailing 1% in Europe while varying geographically within a North-South gradient, ranging from around 0.5% in Northern countries to 2% in Mediterranean area. The incidence is very difficult to estimate accurately as many patients with acute HCV infection are asymptomatic and, thus, do not present for diagnosis. Data from the US report a fall in the annual occurrence of new cases per year from 230,000 in the late 1980s to approximately 35,000 in the 1990s. Therefore, a reduction in incident cases might eventually lead to lower prevalence of HCV infection. Although the incidence of viral infection may be decreasing, the prevalence of liver disease caused by HCV is on the rise. This is due to the significant lag, often 20 years or longer, between the onset of infection and clinical manifestation of liver disease. HCV can be transmitted by a variety of routes. It is most efficiently passed on by large or repeated percutaneous exposures such as through transfusions, transplantation from an infected donor or intravenous drug use. Transmission may also occur from contacts with infected subjects in the household, through perinatal and parenteral exposures in the health care setting. The risk of sexual transmission of HCV is low. Despite this knowledge, nearly half of infected patients do not have a history suggesting a parenteral route of acquisition. Since a prophylactic vaccine is hitherto not available, prevention becomes extremely important: identification of infected persons and of risk factors associated with acquiring HCV allow to develop strategies for preventing the spread of infection as well as its complications, and for planning appropriate care and support services.

Hepatitis C↗