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Biomedical subjects

G Verme

Publications and source records attributed to G Verme.

At least 19 recordsLinked to original sources

Adenine arabinoside monophosphate coupled to lactosaminated human albumin administered for 4 weeks in patients with chronic type B hepatitis decreased viremia without producing significant side effects.

A conjugate of adenine arabinoside monophosphate (ara-AMP) with the liver-targeting molecule lactosaminated human serum albumin (L-HSA) was administered by intravenous infusion for 28 days to eight patients with chronic type B hepatitis. The daily dose varied among the patients, ranging from 34 mg/kg to 53 mg/kg (equal to 1.5 and 2.3 mg/kg ara-AMP, respectively). Pharmacokinetic analysis indicated that, at every dose tested, the conjugate was disposed of without accumulation. Viral DNA serum levels fell markedly during treatment; values rose again when treatment was ceased. The L-HSA-ara-AMP conjugate did not cause either the neurotoxic side effects of free ara-AMP or other adverse clinical reactions. It produced a significant increase both in serum alkaline phosphatase activity and platelet number, and a small but significant decrease in erythrocyte number. These laboratory parameters returned to normal levels within 2 months after treatment. The conjugate induced the production of small amounts of antibodies (approximately 20 pmol of conjugate bound by 1 mL of serum) in one patient only. In conclusion, the present results indicate that the L-HSA-ara-AMP conjugate can exert the antiviral activity of ara-AMP in chronic type B hepatitis patients without producing the neurotoxic side effects which hamper a 4-week period of treatment with the free drug.

Adult

Recurrent necroinflammatory disease of multiple organs and colon. Systemic presentation of inflammatory bowel disease or gut involvement during systemic disorder.

A 30-year-old man with a recurrent febrile illness resembling infection is described. Because he presented with an acute abdomen, he underwent a laparotomy, which showed the paraaortic and mesenteric lymph nodes to be changed into an abscess-like granulomatous tissue made up of necrotized granulocytes. During further flare-ups, the disease affected the spleen, skin, colon, peripheral nerve, and muscle. Histology on the biopsy materials of both the skin and colon, and on the surgically removed spleen showed the same invading pathologic tissue. Exhaustive investigation disclosed no pathogen, and the flare-ups responded repeatedly to high-dose steroids. This patient's picture has recently been defined as a syndrome of chronic granulomatosis based on several published cases. As a distinctive feature, in our patient the granulomas affected also the colon. For the present, and for another previously described similar case we analyzed the factors that might permit the differential diagnosis between the above-mentioned granulomatous syndrome and Crohn's colitis.

Adult

Hepatitis G virus RNA in the serum of patients with elevated gamma glutamyl transpeptidase and alkaline phosphatase: a specific liver disease? [corrected].

We tested the sera of 67 consecutive patients for hepatitis G virus (HGV) RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). These patients (42 males and 25 females, median age 35 years, range 13-64 years) had liver disease of unknown aetiology and were without markers of hepatitis (A-E) viruses or signs of genetically determined, autoimmune, alcoholic or drug-induced liver disease. The controls in this study were 110 patients (50 females and 60 males, median age 45 years, range 9-65 years) with chronic hepatitis B virus (HBV) infection (19 patients) or hepatitis C virus (HCV) infection (91 patients). Ten of 67 (14.9%) patients with cryptogenic disease were positive for HGV RNA by at least three separate tests; HGV RNA was also detected in one of 19 (5.3%) hepatitis B surface antigen (HBsAg) carriers and in nine of 91 (16.6%) patients with antibody to HCV. These data suggest that HGV occurs as frequently in HCV-infected patients as in those with cryptogenic disease. Elevated serum gamma glutamyl transpeptidase (gamma-GT) (higher than twice the normal value) and alkaline phosphatase levels were found in eight of 10 (80%) HGV RNA positive patients and in six of 57 (10.5%) HGV RNA negative patients (P < 0.0001). Five (50%) HGV RNA positive patients had non-specific inflammatory bile duct lesions. A statistically significant difference was observed between HGV RNA positive and negative patients with chronic HBV or HCV infections (P < 0.029). Therefore, the spectrum of liver disease associated with HGV is wide, but a characteristic lesion of the bile duct leading to elevation of cholestatic enzymes might be specific for this virus.

Adolescent

[Is HCV RNA detectable in the ultrafiltrate?].

We investigated by molecular biology the possibility that the HC virus passes by the dialysis membranes into the ultrafiltrate, making the HD monitor a way of HCV transmission. HCV-RNA was tested in blood and in UF samples during 2 HD sessions at T-0, 30, 60, 120 min and at HD end. HCV-RNA was measured by RT-PCR. Viraemia in patients was > 10(-4) gen Eq/ml and remained unchanged along HD, HCV-RNA was not found in whole UF and its x100 concentrates during the HD. We failed to prove the passage of the HCV into the UF, at least in standard conditions.

Hemofiltration

Effect of patient characteristics on hospital costs for cirrhosis: implications for the disease-related group (DRG) reimbursement system.

The Prospective Payment System uses Diagnosis-Related Groups (DRG) as a reimbursement system. DRG 202 is a disease-related group including liver cirrhosis as a whole. Patients referring to the inpatient unit complain of variable severity and complications of cirrhosis, possibly implying different expenditure of resources. Aim of the investigation was to identify factors affecting cost variability in patients with cirrhosis. A total of 73 consecutive, DRG 202-assigned, cirrhotic patients classified according to demographic and clinical variables were evaluated for length and costs of hospitalization calculated on a full-cost basis. Mean length of hospitalization was 10.2 +/- 7 days. Mean cost of hospitalization was Lit. 4.348.000 +/- 2.718.000. Medical, nursing, diagnostic, drug and general charges accounted for 13%, 29%, 37%, 5% and 16% of the cost, respectively. Child-Pugh score significantly correlated with drug consumption (p < 0.005), length (p < 0.01) and costs (p < 0.001) of hospitalization, but not with cost per day. Age, sex, admission status, referral reason, associated diseases and liver transplant susceptibility did not correlate with duration and costs of hospitalization. Disease severity significantly modifies costs of hospital admission in cirrhotic patients mostly on account of longer hospital stay. Surrogate indexes of disease severity, derived from ISTAT/DRG records, cannot identify patients consuming larger resources. In liver cirrhosis, the DRG system could be improved by introducing parameters, such as Child-Pugh score, directly taking into account disease severity.

Adolescent

Recurrent Sweet's syndrome in reactivated Crohn's disease.

A 50-year-old woman developed an acute febrile dermatosis on two occasions concurrently with recurrent Crohn's disease of the colon. Based on the presence of painful erythematous plaques on both hands and forearms, on the leukocytosis with excess bands in peripheral blood, on the histology showing dermal infiltration by mature granulocytes, and on the prompt response to steroids, the diagnosis was made of Sweet's syndrome associated with Crohn's disease. Sweet's syndrome is thought to be a hypersensitivity reaction that leads to parainflammatory (e.g., infections, autoimmune disorders, vaccinations) and paraneoplastic (myeloproliferative disorders, solid malignancy) associations, with a frequency of 10-30%. The association of Sweet's syndrome with Crohn's disease is very rare, but the gastroenterologist should readily differentiate it; it is important to be aware that such patients may have a nonspecific elevated activity index owing to the underlying dermatosis.

Biopsy

The fluctuations of hepatitis C virus RNA and IgM anti-HCV (core) serum levels correlate with those of alanine aminotransferases during the hepatitis relapses of patients treated with interferon.

Variations in the serum levels of hepatitis C virus (HCV) RNA. IgM antibody against the HCV 'core' structural protein (c22) and alanine amino-transferase (ALT) were measured in 23 patients with chronic hepatitis C who underwent therapy with interferon-alpha 2a (IFN alpha 2a). Low pretreatment levels of viraemia and undetectable IgM anti-core were significantly associated with a long-term response to treatment. In patients with hepatitis relapses after the end of treatment, HCV RNA levels increased before or at the same time as ALT in 29 out of 34 cases (85%). ALT flares occurred before or simultaneously with IgM anti-core elevations in 18 out of 20 cases (90%). Therefore, post-treatment hepatitis C exacerbations show the same sequence of events seen as in hepatitis B exacerbations (increases of viraemia followed by those of ALT and IgM anti-'core'). These findings underscore the diagnostic and prognostic usefulness of monitoring anti-HCV-positive patients with quantitative assays for HCV markers.

Alanine Transaminase

Efficacy and safety of interferon alfa therapy in chronic hepatitis C with autoantibodies to liver-kidney microsomes.

Interferon alfa (IFN) therapy is efficacious in chronic viral hepatitides. It may, however, cause adverse immunologic reactions in patients with concomitant autoimmune phenomena. A minority of patients with chronic type C hepatitis have antibodies against liver and kidney microsomes (anti-LKM) in serum. We therefore carried out this study to find out whether IFN is safe and efficacious also in this subgroup. We treated 92 consecutive cases of chronic hepatitis C with IFN. Twelve patients had anti-LKM< and the remaining 80 tested negative to the anti-LKM. The hepatitis C virus (HCV) infection was diagnosed on the basis of positive anti-HCV and HCV-RNA tests. We compared the clinical and virological virological results of the therapy and the side effects found in the two groups. We found that the response to therapy and the outcome after 1 year of follow-up were similar. Treatment was discontinued in one anti-LKM-positive patient because of a drastic increase in ALT levels at the fourth month of therapy. No untoward effect was observed in the other cases. Hepatitis C patients with anti-LKM may be exposed to an increased risk of an adverse hepatitic reaction while being treated with IFN. However, we found that the extent of the risk was minimal compared with the expected benefits of the therapy. IFN is therefore recommended as the first therapy to choose in these patients. They must, however, be monitored more closely for possible liver dysfunction than the ordinary hepatitis C patient.

Adult

Human immunodeficiency virus infection as risk factor for mother-to-child hepatitis C virus transmission; persistence of anti-hepatitis C virus in children is associated with the mother's anti-hepatitis C virus immunoblotting pattern.

To determine the rate of vertical transmission of hepatitis C virus (HCV), we prospectively studied 45 babies born to anti-HCV-positive women with or without concomitant infection with the human immunodeficiency virus (HIV). We performed a second-generation recombinant immunoblotting assay, alanine transaminase (ALT) evaluation, and HCV-RNA testing on sera from 27 infants of HCV+, HIV- mothers and 18 babies of HCV+, HIV+ women, at birth and thereafter. After birth, HCV antibodies progressively disappeared within 12 months in all children but one, whose mother was HCV+, HIV+; this child was the only one who showed detectable levels of HCV-RNA and abnormal ALT values throughout the follow-up (range, 12 to 27 months). Viremia was persistently negative, and ALT levels were continuously normal in the remaining infants, showing that "seronegative" infection with HCV was absent in both groups. Clearance of passively acquired anti-HCV antibodies was found to be slower among babies born to HIV+ mothers (22.3% vs. 3.8% at 12 months, P = .03) and children whose mothers showed three or four anti-HCV reactivities by immunoblotting maintained anti-HCV for longer periods compared with babies born to mothers with one or two anti-HCV reactivities (P = .0001). Seventeen of 27 babies born to HCV+, HIV- mothers were breast-fed, and none of them was infected, confirming the apparent safety for HCV of breast milk. In summary, according to our study, vertical transmission of HCV is an infrequent event, and the presence of HIV in the mother is not an important co-factor for transmission of HCV infection.

Alanine Transaminase

Interferon in chronic hepatitis B.

In patients with typical chronic hepatitis B (HBsAg, HBeAg, HBV-DNA-positive), treatment with interferon-alpha must be carried out for 4-6 months on an alternate-day basis and dosage should be not less than 5 million units/square meter of body surface. The therapeutic response (i.e., clearance of replicative markers, transaminases normalization, histologic improvement) is achieved in about 40% of treated patients and the long-term beneficial effect is maintained in about 90% of them. Oriental HBV carriers, children, immunodeficient and highly viraemic patients are less likely to respond. Patients given combinations therapy (with steroids, antivirals, stimulators of the immune system) do not appear to gain more benefit from the association in comparison with treatment with interferon alone. Side-effects are usually minor (flu-like symptoms), but in a minority major adverse events have also been reported. In conclusion, interferon-alpha is effective in inhibiting viral replication but new therapeutic regimens and a better selection of patients are needed in order to induce persistent remissions and to reduce the cost benefit ratio.

Chronic Disease

Ribavirin treatment for chronic hepatitis D: a pilot study.

To assess whether therapy with Ribavirin may affect the course of chronic delta hepatitis, nine Italian patients with this disease received the drug orally at a dosage of 15 mg/kg daily for 16 weeks. At the end of the therapy period, all patients were followed for 12 additional months. Seven patients completed the trial. Two patients were withdrawn: one developed hemolytic anemia, and the other intractable itching. At the end of treatment HD viremia was reduced in one patient, had cleared in another, and was unchanged in the remaining five patients. None of the patients decreased their alanine transferase (ALT) levels by more than 50%. At the doses given in this study. Ribavirin did not show significant antiviral effects in chronic hepatitis D, and was not effective in reducing the biochemical markers of liver inflammation and necrosis.

Adult

Monoethylglicinexylidide test: a prognostic indicator of survival in cirrhosis.

The aim of this study was to assess the value of the monoethylglicinexylidide assay, a dynamic liver function test based on the determination of the serum concentration of lidocaine major metabolite, as a predictor of survival in cirrhosis. For this purpose, the predictive value of monoethylglicinexylidide was evaluated in comparison with the Pugh score, ascites, encephalopathy and a number of different biochemical parameters as collected from the prospective follow-up of 118 patients with cirrhosis. A stepwise regression analysis was performed on the variables of prognostic value according to the Cox model and with respect to 1-yr survival; because Pugh score and monoethylglicinexylidide were the sole variables selected, they were proved to supply independent prognostic information. The most reliable cutoff values for discrimination between death and survival were 25 ng/ml or less for monoethylglicinexylidide and less than 9 for the Pugh score. In 74 patients without overt signs of liver failure (i.e., Pugh < or = 9), monoethylglicinexylidide provided a wide range of results (i.e., 4 to 77 ng/ml), namely values ranging from very low to elevated. Of the 38 patients with satisfactory Pugh scores (< or = 9) but poor monoethylglicinexylidide values (< or = 25), 11 died during follow-up and 3 underwent liver transplantation, despite having shown no clinical signs of liver failure at entry. On the bases of discriminant levels, the monoethylglicinexylidide test is suitable for adoption as a reliable and sensitive indicator of survival in patients with cirrhosis because it supplies more accurate prognostic information compared with the Pugh score.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Propafenone-induced liver injury: report of a case and review of the literature.

A case of an acute cholestatic syndrome associated with use of the antiarrhythmic drug propafenone is reported here. The close time relationship between the administration of the drug and the acute onset of the liver damage, the histological findings, and the reappearance of biochemical signs of liver dysfunction upon rechallenge with the same medication strongly suggest that propafenone was involved in the pathogenesis of this syndrome. Although rare, hepatotoxicity from this widely used antiarrhythmic medication should be kept in mind in the differential diagnosis of sudden cholestatic syndrome of obscure origin.

Aged