Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe herein the case of a 57-year-old man with thalassemia who developed acute liver failure after undergoing endoscopic injection sclerotherapy (EIS) to control hemorrhage from a ruptured esophageal varix. The patient, who had been confirmed as having liver cirrhosis due to chronic hepatitis C with thalassemia in 1989, was admitted to our department to undergo EIS for esophageal varices, at which time his serum total bilirubin level was 5.5 mg/dl. As a small amount of hematemesis occurred just after a percutaneous transhepatic portography was performed, emergency EIS was carried out, following which the serum total bilirubin level markedly increased, mainly with a direct fraction, until it reached 70 mg/dl. The patient eventually died from acute liver failure with extreme hyperbilirubinemia on the 27th day after experiencing hematemesis despite all treatment. This unfortunate case demonstrates that sclerotherapy could be an inappropriate method of treatment for patients with hemolytic disease.
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PMID:Extreme hyperbilirubinemia induced by endoscopic injection sclerotherapy in a patient with esophageal varices and thalassemia: report of a case. 868 Jan 23

Because of continuous blood transfusions, thalassemia patients are subjected to peroxidative tissue injury by the secondary iron overload. In accordance, analysis of serum from 42 beta-thalassemia patients, aged 4 to 40 years, showed that the mean concentrations of conjugated diene lipid hydroperoxides (CD), lipoperoxides evaluated as malondialdehyde/ thiobarbituric acid (MDA/TBA) adducts, and protein carbonyls increased about twofold with respect to control. Ferritin levels were positively correlated with the amount of MDA (r = .41; P = .007) and showed a positive trend with CD (r = .31; P = .07) and protein carbonyls (r = .35; P = .054), as further evidence of the deleterious effects of high tissue iron levels. Marked changes in the antioxidant pattern were also observed in all patients. Evidence is presented of a net drop in the concentration of ascorbate (-44%), vitamin E (-42%), vitamin A(-44%), beta-carotene (-29%), and lycopene (-67%). On the other hand, an increase of uric acid and bilirubin was observed, whereas serum albumin and glutathione were in the normal range in all patients. As a result, the total serum antioxidant potential, measured as trolox equivalent antioxidant capacity appeared significantly decreased by 14%. Serum levels of vitamin E were inversely correlated with ferritin (r = -.45; P = .003), suggesting a major consumption of this antioxidant under iron overload. Nontransferrin bound iron (NTBI) was in the range 4.5 to 54.8 micrograms/dL (mean, 21.8 +/- 13.9). Although NTBI had a positive trend with ferritin (r = .37, P = .03), no clear correlation was found with either MDA or vitamin E. A mild to severe hepatic damage, as assessed by serum transaminases, was shown in 24 of 42 patients. Serum levels of vitamin E (r = -.49, P = .015), vitamin A (r = -.48, P = .016) and lycopene (r = -.47, P = .020), were inversely correlated with the levels of transminases. On the other hand, lipid-soluble antioxidants in thalassemia patients were depleted to the same extent in hepatitis C virus (HCV)-infected (31 subjects) and in HCV-uninfected (10 subjects), while in the normal range in serum from 30 nonthalassemic patients with HCV-related chronic hepatitis. These results point out that the iron-induced liver damage in thalassemia may play a major role in the depletion of lipid-soluble antioxidants. The variations of the parameters evaluated in the present study were not correlated with the age of the patients. Our results suggest that the measurement of peroxidation products, matched with evaluation of antioxidants, may be a simple measure of iron toxicity in thalessemia, in addition to the conventional indices of iron status.
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PMID:Oxidative stress and antioxidant status in beta-thalassemia major: iron overload and depletion of lipid-soluble antioxidants. 889 30

Forty-eight household contacts of 25 children with homozygous beta-thalassaemia and chronic hepatitis C (index cases) were evaluated for antibodies against hepatitis C virus (HCV) and increased transaminase values in the blood. The mean age +/- SD of the household contacts was 36.4 +/- 17.0 years (range 5-67) and 20 of them were males. All thalassaemic patients (age 14.3 +/- 3.0 years, range 8-19) were positive for anti-HCV antibodies by repeated determinations. HCV-RNA was detected in the blood of 22 of 23 patients tested by polymerase chain reaction. Liver biopsies were performed in 18 patients and showed chronic active hepatitis in 14 and chronic persistent hepatitis in 4. The mean duration of contact between the index cases and the household contacts while the index cases were anti-HCV positive was 45.3 +/- 10.2 months (range 17-57). None of the household contacts was found to be positive for anti-HCV antibodies nor did they have elevated transaminases in the two examinations performed within an interval of about 2 years. Among the HCV-negative household contacts are included 14 who mentioned needlestick injuries with needles used by the index cases.
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PMID:Lack of transmission of hepatitis C in household contacts of children with homozygous beta-thalassaemia. 906 12

A 35 year old man with a fatal Campylobacter jejuni infection is described. He had HbE/beta zero thalassaemia and had undergone splenectomy nine months previously for hypersplenism; he also had chronic hepatitis C infection. He presented with high grade fever but no gastrointestinal symptoms and rapidly progressed to septicaemic shock and hepatic encephalopathy despite treatment with penicillin, gentamicin, and, later, chloramphenicol and ceftazidime. Only one case of Campylobacter jejuni septicaemia occurring post-splenectomy has been reported previously, also in an iron overloaded thalassaemia patient. Unusual Gram negative bacilli must be covered by the chosen antibiotic regimen when splenectomised thalassaemic patients present with high grade fever.
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PMID:Fatal Campylobacter jejuni infection in a patient splenectomised for thalassaemia. 921 30

No experience has been reported to date in treating chronic hepatitis C virus (HCV) infection with interferon (IFN) therapy after BMT, mainly due to concerns related to the impact of an immunomodulatory drug in patients who are immunologic and haematologic chimeras. However, chronic inflammatory activity related to HCV infection results in a chronic fibrogenous mechanism potentially leading to liver cirrhosis and hepatocellular carcinoma. Moreover, patients transplanted for beta-thalassemia could be at greater risk because of concomitant iron overload and pre-existing fibrous liver damage. Eleven patients with serological, biochemical, histological and molecular biological evidence of HCV infection were included in the study and treated for 6-12 months with recombinant IFN 24-65 months following BMT. The serum alanine aminotransferase (ALT) was persistently elevated (range 85-1242 U/l; mean 416) for at least 1 year prior to IFN treatment. Ten patients completed the protocol; five were considered as responders to treatment. In these five patients the liver histology showed an overall reduction of inflammation and necrosis: histological inflammatory activity improved from chronic active hepatitis (CAH) to chronic persistent hepatitis (three patients) or minimal residual inflammatory activity (two patients). The Knodell total activity score varied from 5.4 (range 3-9) to 1.4 (range 1-2; P = 0.05). All responding patients revealed negativization of serum HCV-RNA, that has been persistent in four (follow-up 1-3 years). ALT level fell to 15-80 U/l (mean 52; P = 0.0027). No major complications occurred during the therapy and no influence on marrow engraftment parameters were noted. We conclude that IFN therapy does not adversely interfere with engraftment and that it is a feasible therapy for treatment of chronic hepatitis C virus after BMT.
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PMID:Alpha-interferon treatment of chronic hepatitis C after bone marrow transplantation for homozygous beta-thalassemia. 938 79

Polytransfused patients represent a major risk group for hepatitis C (HCV) acquirement. Haemophiliacs and thalassemic patients treated with virus contaminated blood or blood derivatives frequently exhibit anti-HCV antibodies and signs of chronic hepatitis. The serological profile for the HCV infection was investigated in 13 haemophiliacs, 18 cases of thalassemia and in 14 polytransfused patients affected by other diseases. The presence of anti-HCV antibodies was detected by means of the ORTHO HCV 3.0 ELISA kit and confirmed by Western-blot Murex. The serotyping used synthetic peptides mimicking the immunodominant epitopes in the NS4 region, characteristic of each of the six HCV genotypes in an ELISA blocking reaction (Murex). Serotype 1 was prevalent (51.1%), while serotype 2 was detected in 13.3% of patients, with a higher frequency in thalassemia cases. The remaining samples were multireactive, and serotype 3 alone was not detected. The profile of Western-blot bands was distinct for the monoreactive samples belonging to serotype 1 or 2. The analysis of the multireactive samples in young (thalassemic, age mean 15.17 +/- 6.5) and aged patients (haemophiliacs, age mean 32.64 +/- 13.5) allows us to suggest a different succession of reinfection acquirements. The infection with one of the subtypes does not confer protection against the reinfection with others. However, a certain attenuation of the symptomatology is obvious in the case of reinfections, indicating the existence of crossantigenic reactivities which contribute to protection. This protection is more evident in the case of primary infection with type 2 and is partially due to antigens coded by the NS4 genomic segment.
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PMID:Serological profile assessment of the infection with hepatitis C virus (HCV) in haemophiliacs and thalassemic patients. 949 79

The aim of this study was to investigate the prevalence of HCV genotypes among Greek patients with chronic hepatitis C and to assess the influence of genotypes and quasi-species populations on efficacy of interferon therapy. Genotypes were determined in 65 patients (18 patients after kidney transplantation, 16 with thalassemia and 31 with no known risk factor) with elevated ALT for more than 6 months and histologically proven chronic hepatitis, using the Inno-Lipa strip assay. The quasi-species were determined using the fluorescence single-strand conformational polymorphism method. Most patients were infected with genotype 3a, namely 61% of patients with kidney transplants (n = 18), 50% of patients with thalassemia (n = 16) and 48% of patients without known risk factors (n = 31). Other genotypes were found including coinfection with different genotypes. In all patients with mixed infection, genotype 3a was present. Thirty-six patients from the last two groups received interferon (3Mio U 3x week) for 1 year. Biochemical and/or virological and histological responses were found in 11/19 patients with genotype 3a (58%), 3/5 with mixed infection, 2/4 with genotype 1b, 2/5 with genotype 2a, 1/4 with genotype 1a and 1/1 with genotype 4. The virus found in non-responders with genotype 3a was genetically more heterogeneous than in responders. These data indicate that (1) the genotype 3a is prevalent in Greek patients (68% of all patients), (2) there is no significant difference regarding genotypes among patients with different risk factors and (3) although based on a small number of patients, the genotype 3a seems to respond better to interferon therapy. Finally, the number of quasi-species may be a factor predictive of response.
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PMID:Genotype distribution of hepatitis C virus infection in Greece: correlation with different risk factors and response to interferon therapy. 951 57

Twelve patients with anemias and their close relatives were examined: 8 adults (3 men and 5 women) and 4 children (3 boys and 1 girl). Six of them were Armenians, 1 woman was Russian, and the rest were of mixed origin: 3 Russian-Azerbaijan-Ukrainian, 1 child Russian-Ukrainian-African, and 1 woman Russian-Ukrainian. Hemoglobinopathies were detected in 10 subjects from 4 families (3 families from Donetsk and 1 from Moscow). Homozygotic beta-thalassemia major (Hb F 98.9%) was diagnosed in a 2-year-old Armenian girl from Donetsk. The girl lags behind in development and suffers from anemia with hepatosplenomegaly and jaundice. Heterozygotic beta-thalassemia minor with increased levels of Hb A2 and Hb F was diagnosed in her parents (Armenians from Azerbaijan). A 15-year-old Russian-Azerbaijan-Ukrainian boy from another family in Donetsk had beta-thalassemia with HbD (94%). The boy suffers from anemia with hepatosplenomegaly, jaundice, and chronic hepatitis. Heterozygotic beta-thalassemia with increased levels of Hb A2 and Hb F was revealed in proband's mother and brother; the father was not examined. alpha-Thalassemia is suspected in a 3-year-old boy from a Russian-Ukrainian-African family in Donetsk; he presented with a very small "fast" abnormal hemoglobin fraction. The boy suffers from anemia with splenomegaly and systolic murmur. Blurred form of thalassemia minor is diagnosed in the mother. The father, an African from Zaire, was not examined. Heterozygotic beta-thalassemia with increased Hb A2 level was revealed in a 20-year-old Armenian boy from Moscow. He presented with manifest splenomegaly, chronic gastritis, and mitral valve prolapse. His mother suffers from thalassemia minor, was anemic during pregnancy, and there are cases of anemia in the family. No hematologic disorders were found in the father. No hemoglobinopathies were detected in a 59-year-old Russian women from the town of Tver with very grave anemia; apparently, her condition was acquired, but not hereditary. Data on patients in the city of Donetsk are of special interest, for there are virtually no reports about hemoglobinopathies in the Ukraine.
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PMID:[Beta-thalassemia and Hb D in patients with anemia]. 957 28

After successful marrow transplantation (BMT) iron overload remains an important cause of morbidity in Thalassemia. After BMT, patients have normal erythropoiesis capable of producing a hyperplastic response to phlebotomy so that this procedure can be contemplated as a method of mobilizing iron from overloaded tissues. Forty-one patients (mean age 16 +/- 2.9 years) with prolonged follow-up (range 2-7 years) after BMT were submitted to a moderate intensity phlebotomy program (6 ml/kg blood withdrawal at 14-day intervals) to reduce iron overload. Values are expressed as mean +/- SD or as median with a range (25th-75th percentile). Serum ferritin decreased from 2,587 (2,129-4,817) to 280 (132-920) micrograms/l (p < 0.0001), total transferrin increased from 2.34 +/- 0.37 to 2.9 +/- 0.66 g/l (p = 0.0001), transferrin saturation decreased from 90% +/- 14% to 39% +/- 34% (p < 0.0001). Liver iron concentration evaluated on liver biopsy specimens decreased from 20.8 (15.5-28.1) to 3 (0.9-14.6) mg/g dry weight (p < 0.0001). Alanine amino-transaminase from 5.2 +/- 3.4 to 1.6 +/- 1.2 (p < 0.0001) times the upper level of normality. The histological grading for chronic hepatitis (Histology Activity Index) decreased from 4.2 +/- 2.4 to 2.3 +/- 1.8 (p < 0.0001). Phlebotomy is a safe, efficient, and widely applicable method to decrease iron overload in "ex-thalassemic."
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PMID:Treatment of iron overload in the "ex-thalassemic". Report from the phlebotomy program. 966 50

Hepatitis C virus is responsible for the majority of cases of post-transfusion non-A non-B hepatitis in patients with thalassemia major. Interferon alfa is an effective treatment for patients with chronic hepatitis C. Response to therapy is related to the duration of treatment, the viral load in serum, and the hepatitis C virus genotype. The purpose of this study was to estimate the response of multitransfused children with beta-thalassemia and chronic hepatitis C to interferon alfa-2b therapy. Thirteen patients with beta-thalassemia and chronic hepatitis C, (mean age+/-SD, 14.1 +/- 1.7 years) participated in the study. Liver biopsy, estimation of HCV RNA, and virus genotyping were performed before onset of treatment. All patients were positive for HCV RNA in a low concentration; two patients carried the la genotype, four had genotype 3, and seven had genotype 4. Patients were treated with 3 x 10(6) U of subcutaneous interferon alfa-2b three times weekly. Eleven of 13 patients received therapy for 18 months; the remaining two underwent therapy for 6 months. Six of 13 patients responded completely to therapy, four responded partially, and three did not respond at all. The grade of inflammation and stage of fibrosis was lower in complete responders. Complete responders had lower ferritin values compared with the values for partial and nonresponders before starting therapy. The results suggest that interferon therapy should be recommended for children with beta-thalassemia major complicated by a low viral concentration of hepatitis C.
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PMID:Response to interferon alfa-2b therapy in mutitransfused children with beta-thalassemia and chronic hepatitis C. 1058 97


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