Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of factor VIII concentrates has greatly facilitated hemophilia care and has made the home care of hemophilia possible. However, factor VIII concentrate that has been produced using traditional methods contains large amounts of foreign proteins and viruses. This has resulted in the development of immunologic abnormalities in many hemophiliacs and has exposed many of these patients to blood-borne viruses such as the human immunodeficiency virus (HIV) and hepatitis viruses. Factor VIII circulates in plasma in complex with the von Willebrand factor (vWF). Both factor VIII and vWF have been purified and monoclonal antibodies (mAb) have been generated to both of these proteins. When bound to a solid support, these mAb's can be used to isolate selectively the proteins of interest. Recently, two separate procedures have been used in the immunoaffinity purification of factor VIII on a commercial scale. One product (Monoclate) has been prepared using a mAb to the vWF bound to a chromatography column. The other product (Hemophil M) uses immobilized mAb to the factor VIII molecule. Factor VIII concentrate purified using either of these approaches is far more pure than traditional factor VIII concentrates. In addition, the use of both viral purification and viral inactivation procedures has greatly reduced the risk of viral contamination. Early clinical studies have demonstrated that these products are effective in treating bleeding episodes and that the risk of viral infection with HIV or hepatitis viruses is low. Factor VIII concentrate produced using mAb technology appears to be the product of choice in previously untransfused hemophiliacs. Its role in the treatment of patients who have already been infected with HIV is less clear.
 ...
PMID:Immunoaffinity purification of factor VIII. 250 62

The introduction of factor VIII and IX concentrates in the early 1960s brought a significant change in the hemophiliac's life. In consequence hemophilia treatment has been improving rapidly since, and today most life-threatening hemorrhages are controlled by replacement therapy. Hemophilic arthropathy through recurrent joint and muscle bleedings occurs later in life and is often limited to one joint only. Major surgery in hemophiliacs involves little more risk than in non-hemophilic patients, provided of course there is close teamwork between surgeon and hematologist. The most frequent causes of death are no longer hemorrhages but blood-product-associated AIDS and hepatic failure. Fortunately these side effects have been overcome by the use of virus-inactivated concentrates which in Switzerland have been generally administered since 1986. Factor VIII and IX concentrates must contain a precisely declared quantity of factor VIII and IX activity respectively, with a high specific activity. High-purity concentrates should be preferred because of the hazardous effect of foreign proteins administered intravenously in large quantities over a long period. Activation of fibrinolysis with consequent failure of hemostasis or even worsening of hemorrhage may be a clinically relevant side-effect of DDAVP therapy. When DDAVP is used for prophylactic treatment before surgery, an interval of one hour between the intravenous administration of DDAVP and surgery ensures the latter is performed at the time of highest factor VIII and von Willebrand factor level but with already decreased t-PA and fibrinolytic activity. If DDAVP is used in case of hemorrhage or postoperatively, however, the whole fibrinolytic potential must be taken into account. In these cases subcutaneous administration is advantageous due to more protracted t-PA release and the subsequent lower fibrinolytic activity, which can more easily be neutralized by tranexamic acid. To prevent hemophilic arthropathy, correct replacement therapy in hemarthroses is essential: it should be performed as early as possible, preferably in a home therapy program; adequate levels of factor VIII or IX should be achieved and maintained over a sufficient length of time. Hemophiliacs who did not receive replacement therapy during childhood often need major surgery because of severely destructed joints. Joint replacement by total knee and hip prostheses has proved very successful if certain special conditions are fulfilled. Surgical indications should, however, be carefully considered and the possibilities and limits of replacement therapy should be well known. Blood-product-associated hepatitis will be of prognostic relevance in many hemophiliacs treated formerly with non-virus-inactivated concentrates.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Current clinical aspects in hemophilia treatment]. 250 19

Seventeen previously untreated boys with haemophilia A were treated with high purity heat treated factor VIII concentrate (8Y) for up to 36 months. Liver function tests were assessed monthly. No boy's serum has been shown to contain HIV antibodies and no increases in alanine transaminase activity have been detected. In only one patient was a single rise in aspartate transaminase activity noted, and this was without a corresponding rise in alanine transaminase. A second patient's serum contained hepatitis B core antibody transiently. It was thought likely in both cases that the abnormalities reflected intercurrent infections rather than disease associated with transfusion. The physical treatments used in the production of 8Y seem to inactivate the agent(s) responsible for non-A, non-B hepatitis and HIV transmission by transfusion of factor VIII has been abolished. There are, however, problems associated with conducting safety trials in young haemophiliac patients.
 ...
PMID:Safety trial of heated factor VIII concentrate (8Y). 251 Jun 7

Six intraoperative blood samples were obtained at intervals from each of 100 individuals undergoing their first liver transplants. The patients fell into the following diagnostic categories: postnecrotic cirrhosis 28, primary biliary cirrhosis 20, sclerosing cholangitis 19, miscellaneous diseases 14, carcinoma/neoplasia 12 and fulminant hepatitis 7. Coagulation factor values in the initial (baseline) blood samples varied by patient diagnosis. In general, all factor levels were reduced except factor VIII:C, which was increased to almost twice normal. The slight intraoperative changes in factors II, VII, IX, X, XI and XII suggested that a steady-state relationship existed between depletion (consumption/bleeding) and repletion (transfusion, transit from extra- to intravascular space), even in the anhepatic state. In contrast, there were rapid and very significant falls in factor VIII and fibrinogen and a less pronounced decrease in factor V, all reaching their nadirs in early to mid-Stage III. The cause of these coagulation changes appears to be activation of the fibrinolytic system.
 ...
PMID:Liver transplantation: intraoperative changes in coagulation factors in 100 first transplants. 265 Dec 69

Since 1982, when the World Federation of Hemophilia first published a document on the state of the art of hemophilia diagnosis and care, there have been lights and shadows in this field. Although the widespread infection of hemophiliacs with the human immunodeficiency virus (HIV) contaminating clotting factor concentrates is still a threatening and formidable shadow, the gloomy picture brought about by the AIDS epidemic is partially lightened by spectacular improvements in therapy and diagnosis. Carrier detection and first-trimester prenatal diagnosis can now be performed accurately in most kindreds by analysis of DNA of the factor VIII or IX genes. An important step forward towards the elimination of the risk of blood-borne infections transmitted by plasma products was recently made through the application of virucidal methods to clotting factor concentrates. Since HIV appears more vulnerable to such methods than the hepatitis viruses, currently available concentrates can be considered substantially free from the risk of transmitting HIV infection. Even though transmission of hepatitis is much reduced but not totally abolished, virucidal methods are continuously being improved, so that it can be foreseen that concentrates will become safer and safer. Finally, factor VIII produced by recombinant DNA technology is undergoing the first clinical trials in hemophiliacs. Hopefully, it will free from the risk of transmitting infections and will be available in sufficiently large amounts to meet the need of hemophiliacs worldwide. In 1982, the World Federation of Hemophilia published a message on the status of diagnosis and treatment of hemophilia. Since then, hemophilia care has been complicated by widespread infection of hemophiliacs with human immunodeficiency virus (HIV).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hemophilia: state of the art of hematologic care 1988. 265 17

In-vitro and animal studies have shown that viral agents can be removed from or inactivated in clotting factor concentrates by physical or chemical treatment. However, clinical data have as yet not substantiated the results of these studies. 13 haemophilia A patients who had not been treated previously with blood or blood products were given a dry-heated factor VIII concentrate and were tested serologically over the next 12 months. Hepatitis developed in 11 patients (84%) and was invariably of type non-A, non-B. Morbidity was not related to the lot of the therapeutic material or to the number of infusions. The incubation period was either 5 or 8-11 weeks, and only 1 patient had symptoms. Aminotransferase elevation showed both monophasic and biphasic patterns. During the follow-up period signs of the disease disappeared in 10 patients (90%). These findings contrast with the absence of non-A, non-B hepatitis in chimpanzees given the same heated concentrate. Thus, clinical studies in first-exposure haemophiliacs are essential for the true evaluation of the safety of new "treated" concentrates.
 ...
PMID:Transmission of non-A, non-B hepatitis by heat-treated factor VIII concentrate. 286 54

The main causes of hepatitis transmission by blood products are hepatitis B and non A non B hepatitis (NANB). A reduction in hepatitis transmission has been achieved by screening blood donors for hepatitis B surface antigen, but it is not known what the effectiveness of screening donors for raised plasma alanine aminotransferase levels or hepatitis B core antibody will be. Attempts to reduce NANB hepatitis transmission have mainly focussed on heat treatment of factor VIII and IX concentrations, and preliminary data suggests that under certain heating conditions inactivation of the NANBvims occurs. Although albuminoid preparations are known not to transmit hepatitis, three immunoglobulin preparations for intravenous administration (IV IgG) have transmitted hepatitis, suggesting that the inclusion of a terminal virucidal step is essential.
 ...
PMID:Hepatitis transmission by blood products. 289 2

The safety of an antihaemophilic factor concentrate treated with the organic solvent tri-(n-butyl)phosphate and sodium cholate (factor VIII-SD) was assessed for transmission of non-A, non-B (NANB) hepatitis and human immunodeficiency virus (HIV). Patients enrolled in the study had no previous exposure to blood products made from plasma pools, although 5 had received small quantities of single-donor products. All but 1 had normal alanine aminotransferase (ALT) levels, none had markers of HIV infection, and all had been vaccinated against hepatitis B. After treatment with factor VIII-SD, serum ALT levels and HIV antibody were monitored for up to 1 year. 20 patients received 625 to greater than 40,000 U (total 163,000 U, median dose 3900 U), and 17 of these were followed up for at least 6 months: transmission of either NANB hepatitis or HIV was not observed.
 ...
PMID:Virus safety of solvent/detergent-treated antihaemophilic factor concentrate. 289 62

32 patients with coagulation factor deficiencies and likely to be susceptible to non-A, non-B hepatitis (NANBH) virus infection were treated with a total of 20 batches of a factor VIII concentrate and 10 batches of a factor IX concentrate, both heated at 80 degrees C for 72 h in the freeze-dried state. Serial measurements of serum aminotransferase levels for 4 months revealed no patterns of rises attributable to NANBH. Severe dry heating appears to have reduced the risk of NANBH transmission from about 90% in untreated concentrates to a statistically determined rate of 0-9%. No evidence was found in recipients of infection with hepatitis B or human immunodeficiency virus.
 ...
PMID:Effect of dry-heating of coagulation factor concentrates at 80 degrees C for 72 hours on transmission of non-A, non-B hepatitis. Study Group of the UK Haemophilia Centre Directors on Surveillance of Virus Transmission by Concentrates. 290 65

Posttransfusion non-A, non-B hepatitis associated with the formation of hepatocyte cytoplasmic tubules was experimentally transmitted to chimpanzees by intravenous inoculation of a proven-infectious plasma that had been pelleted and microfiltrated, or purified by a combination of pelleting and rate-zonal banding. The results of these studies indicate that a factor VIII-derived non-A, non-B tubule-forming agent will pass through an 80-nm membrane filter and that it can be recovered from infected plasma by use of a purification procedure that assumes the non-A, non-B tubule-forming agent is a small, enveloped virus. Our findings, in combination with the known sensitivity of the non-A, non-B tubule-forming agent to chloroform and its apparent lack of nucleic acid homology with hepatitis B virus, further suggest that at least one etiologic agent of human posttransfusion non-A, non-B hepatitis may be a small, enveloped RNA virus.
 ...
PMID:Posttransfusion non-A, non-B hepatitis in chimpanzees. Physicochemical evidence that the tubule-forming agent is a small, enveloped virus. 298 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>