Gene/Protein
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Drug
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Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
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Query: UMLS:C0019693 (
HIV
)
170,526
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Three patients with acute thrombotic thrombocytopenic purpura (TTP) (one associated with E. coli infection) received as primary treatment pooled fresh frozen plasma (FFP) virus inactivated by the solvent/detergent (SD) method, plus prednisolone. All three patients attained platelet counts of > 50 x 10(9)/l by days 7, 3 and 10, respectively. Serum creatinine became corrected in parallel. Neurological features were slow to resolve in one patient, and developed de novo during plasma infusion in another with rapid reversal once intensive plasma exchange with SDFFP was instituted. All patients are in stable remission > 1 years later. SDFFP was well tolerated with no febrile or other reactions, and all patients remained negative for markers of infection with
HIV
, hepatitis B and hepatitis C viruses. One patient was positive for antibodies for
hepatitis A
virus and parvovirus B19 prior to treatment. The other two patients remained antibody negative at the end of therapy.
...
PMID:Solvent/detergent fresh frozen plasma as primary treatment of acute thrombotic thrombocytopenic purpura. 1034 71
Viral hepatitis is a persisting concern. Outbreaks of
hepatitis A
occur in developed countries where only 10% to 20% of the population is seroprotected. The disease may cause fulminant liver failure and death. People who are targeted for vaccination include intravenous drug users, homosexuals, and chronic hepatitis patients. Secondary prophylaxis of household contacts is an efficient way to prevent secondary cases. Universal vaccination is now in progress for hepatitis B. Vaccination failure may occur in low birth weight infants, or in infants infected in utero. Chronic carriers of viral hepatitis may progress to cirrhosis and hepatocarcinoma, the latter risk being most important for men infected at birth. Alcohol intake should be avoided in carrier adolescents. Interferon is able to triple the rate of hepatitis B e antigen loss and decouple the rate of hepatitis B s antigen loss after one year, shortening disease evolution and, it is to be hoped, decreasing the risk of unfavorable outcome. Similarly, lamivudine increases by four times the rate of hepatitis B e antigen loss in adults. However, precore mutants may be selected by immune pressure after seroconversion in children, and tyrosine-methionine-aspartate-aspartate (YMDD) mutations appear in 15% of patients treated with lamivudine after 1 year. Hepatitis C is mainly acquired during childhood via true vertical transmission. The risk of acquiring Hepatitis C is related to the presence and amount of RNA for hepatitis C virus in mothers at the time of birth. The infection rate for the hepatitis C virus is higher in children from mothers who have tested positive for
HIV
, and higher if these children are themselves coinfected with
HIV
. Treatment with interferon alone has a poor rate of efficiency, although pediatric studies remain scarce. Combination treatment using ribavirin plus interferon yield a higher rate of success in eradicating viral infection in adults.
...
PMID:Update on prevention and treatment of viral hepatitis in children. 1055 88
Various methods are described for the elimination of infectious viruses from activated prothrombin complex concentrates (aPCCs) and for the analysis of the final products (AUTOPLEX T and FEIBA VH). Viruses of concern in human plasma-derived products are enveloped (hepatitis B and C, cytomegalovirus, Epstein-Barr virus, and human immunodeficiency virus [
HIV
]) and nonenveloped (
hepatitis A
and parvovirus B19). Donated blood used for AUTOPLEX T is screened for antihepatitis C, HBsAg, anti-
HIV
types 1 and 2, and p24 antigen. Plasma pools utilized for raw materials are also tested by PCR for
HIV
and hepatitis C virus. Partial virus inactivation and partitioning are achieved by purification of the aPCC. Further reduction of virus infectivity is accomplished by lyophilization and dry-heat treatment. Each step undergoes virus elimination validation studies in which a relevant sample is 'spiked' with the appropriate virus or model virus. The total reduction in virus from raw material to final product can then be calculated. For AUTOPLEX T the cumulative log10 reduction factors for several viruses vary from 4.2 to 14.3. This ensures an exceptionally high margin of safety. Definitive evidence for product safety was obtained by clinical observation of treated patients. The viral inactivation process of AUTOPLEX T involves a four-tier viral safety program, including Cohn alcohol fractionation and dry-heat treatment, in place of the two-stage vapour-heating process for FEIBA.
...
PMID:Efficacy of viral clearance methods used in the manufacture of activated prothrombin complex concentrates: focus on AUTOPLEX T. 1059 84
Over the last decade, more than 300 phase I and phase II gene-based clinical trials have been conducted worldwide for the treatment of cancer and monogenic disorders. Lately, these trials have been extended to the treatment of AIDS and, to a lesser extent, cardiovascular diseases. There are 27 currently active gene therapy protocols for the treatment of
HIV
-1 infection in the USA. Preclinical studies are currently in progress to evaluate the possibility of increasing the number of gene therapy clinical trials for cardiopathies, and of beginning new gene therapy programs for neurologic illnesses, autoimmuno diseases, allergies, regeneration of tissues, and to implement procedures of allogeneic tissues or cell transplantation. In addition, gene transfer technology has allowed for the development of innovative vaccine design, known as genetic immunization. This technique has already been applied in the AIDS vaccine programs in the USA. These programs aim to confer protective immunity against
HIV
-1 transmission to individuals who are at risk of infection. Research programs have also been considered to develop therapeutic vaccines for patients with AIDS and generate either preventive or therapeutic vaccines against malaria, tuberculosis,
hepatitis A
, B and C viruses, influenza virus, La Crosse virus, and Ebola virus. The potential therapeutic applications of gene transfer technology are enormous. However, the effectiveness of gene therapy programs is still questioned. Furthermore, there is growing concern over the matter of safety of gene delivery and controversy has arisen over the proposal to begin in utero gene therapy clinical trials for the treatment of inherited genetic disorders. From this standpoint, despite the latest significant achievements reported in vector design, it is not possible to predict to what extent gene therapeutic interventions will be effective in patients, and in what time frame.
...
PMID:Latest developments in gene transfer technology: achievements, perspectives, and controversies over therapeutic applications. 1066 69
In the early 1990s, a series of outbreaks of hepatitis C (HCV) infections clustering among recipients of certain lots of plasma-derived medicinal products (PDMP) alarmed regulatory authorities, manufacturers and the public alike. Also, a few episodes of
Hepatitis A
(HAV) infections occurred in haemophiliacs receiving solvent-detergent-treated factor VIII concentrates. Thus, several measures were brought into effect to reestablish the safety of the incriminated products and to further increase the margin of safety of PDMP in general. Therefore, intramuscular immunoglobulins had to be free of HCV RNA as shown by nucleic acid amplification technology (NAT) in the final products. Furthermore, the manufacturing process of PDMP had to be validated for both viral inactivation and elimination. Finally, HCV-NAT was to be standardised and implemented as a validated test of plasma pool samples. In 1994, a joint meeting of EPFA, EAPPI and Regulatory Authorities was held in Brussels to outline the state of the art and to delineate the actions to be taken. Five years later, in 1999, the incidence rates of
HIV
, HBV and HCV in unpaid blood donors have been minimized, especially in European countries. With probabilities for window period donations as low as 0.6 in 1 million for both
HIV
and HCV and 2.1 in 1 million for HBV in Switzerland, labile blood products have reached extreme, but not absolute safety. The introduction of HCV-NAT roughly doubles this safety resulting in a 1 in 3 million probability of a window donation.Concomittantly, extensive viral validation studies document effective inactivation and removal of viruses in PDMP. The demonstrated margins of safety, expressed as logarithmical reduction factors (LRF), range from 4 to over 20 log(10), depending on product, virus, and inactivation procedure used. Further progress to even safer PDMP shall be acomplished by consolidating the GMP processes, abandoning of obsolete requirements and harmonising national regulations within Europe. Before introducing new measures for additional agents such as HAV or Parvovirus B 19, gains and risks and even potential new threats have to be carefully assessed. Alternative efforts for the safeguard of patients, e.g. vaccination for HAV, need to be balanced against the risks of changing established and validated manufacturing procedures of PDMP with long-lasting safety records.
...
PMID:Assessment of needs for plasma for fractionation in Europe. 1068 61
The objective of this overview is to assess the present situation with regards to gastrointestinal and hepatobiliary diseases prevailing in Thailand. In that context, special emphasis has been put on those forms of viral hepatitis prevalent in the region, namely,
hepatitis A
the frequency of which has undergone a change from hyper- to hypoendemic with a resulting decline in naturally acquired immunity; hepatitis B with its tendency to cause chronic liver disease mainly due to asymptomatic infections during early childhood and the impact of mass vaccination programs on its endemicity; hepatitis C which can also lead to chronicity; hepatitis D solely found as a coinfection with hepatitis B; hepatitis E acute cases of which can sporadically be found; hepatitis G encountered in healthy subjects at a prevalence similar to that seen in patients with chronic liver disease and rather more prevalent among people at risk for contracting blood borne agents; finally the novel hepatitis TT virus with a distribution comparable to that of hepatitis G virus and a similarly unclear role as to the etiology of serious liver disease. Particularly in connection with hepatitis B we have examined the situation regarding hepatocellular carcinoma which represents one of the most common malignancies among the Thai population. Cholangiocarcinoma caused by the liver fluke Opisthorchis viverrini is the most common form of liver cancer in the northeastern part of Thailand where an estimated 70% of the population are infested with the parasite. Peptic ulcer caused by Helicobacter pylori constitutes another common gastrointestinal affliction with the overall prevalence of antibodies to the agent amounting to 63 to 74% in patients exhibiting gastroduodenal symptoms. The final part of the paper deals with
HIV
-related gastrointestinal and liver disease and with amebic and pyogenic liver abscesses.
...
PMID:Current status of infection-related gastrointestinal and hepatobiliary diseases in Thailand. 1069 96
Individuals with Haemophilia are at risk from
hepatitis A
virus (HAV) infection through exposure to blood products. Havrix(R), an intramuscular
hepatitis A
vaccine, is currently recommended for the prevention of disease caused by
hepatitis A
virus. Because bleeding may complicate intramuscular injections in those with bleeding disorders, we conducted a randomized, Phase IV clinical trial to compare the safety and immunogenicity of Havrix(R) given by the subcutaneous (s.c) vs. intramuscular (i.m.) route. A total of 45 children with Haemophilia were vaccinated subcutaneously, while their 41 nonhaemophlic siblings were vaccinated intramuscularly, at a dose of 720 Elisa units (EL.U.) at time 0 and 6 months. All children were anti-HAV and anti-
HIV
negative at baseline, and the haemophilic group did not differ from their siblings in alanine aminotransferase (ALT; 25 IU L-1 vs. 22 IU L-1), or in age; 8.5 years vs. 8.7 years. The vaccine was well tolerated, with minor adverse events being similar between groups; 21 (47%) vs. 24 (58%), P > 0.05. Local symptoms included soreness in 39 (45%), erythema in 25 (29%), swelling in 21 (24%), and bruising in six (7%), with no differences between groups. The proportion seroconverting to anti-HAV IgG positive did not differ between groups; 98% vs. 97% at month 1; 82% vs. 93% at month 6; and 100% vs. 100% at month 8, respectively. The HAV geometric mean titre was lower in those with Haemophilia, 185 vs. 233 mIU mL-1 at month 1; 68 vs. 94 mIU mL-1 at month 6; and 584 vs. 1082 mIU mL-1 at month 8, respectively. We conclude that Havrix(R) is safe and immunogenic when administered s. c. in children with Haemophilia.
...
PMID:Safety and immunogenicity of subcutaneous hepatitis A vaccine in children with haemophilia. 1078 Nov 96
We report the case of two patients in whom acute hepatitis A was associated with a marked and prolonged increase in human immunodeficiency virus type 1 (HIV-1) viral load. Although in one patient the rise in
HIV
-1 RNA might also have been related to the interruption of antiretroviral therapy, we also observed a similar pattern in the other patient who had a stable undetectable plasma viraemia prior to acute hepatitis and never received treatment with anti-retrovirals. Our observation supports the hypothesis that immune activation that is induced by acute hepatitis A virus (HAV) infection may trigger
HIV
-1 replication. This highlights the importance of maintaining antiretroviral therapy throughout the acute phase of
hepatitis A
and of preventing HAV infection through active immunization.
...
PMID:Persisting HIV-1 replication triggered by acute hepatitis A virus infection. 1084 87
The objectives of this study were to investigate the prevalence of infections with hepatotrophic viruses in an anti-human immunodeficiency virus (HIV)-positive population from Buenos Aires and to compare it among the main risk groups for
HIV infection
. Four hundred and eighty-four consecutive patients attending the HIV outpatients clinic were studied: 359 men and 125 women, median age 29 years (range 16-67 years); 35.5% had presented acquired immune deficiency syndrome (AIDS)-defining conditions. Two hundred and thirty-four patients were intravenous drug users (IVDU), 99 had homosexual and 142 heterosexual preference, seven had received blood transfusions and two had no risk factors. Hepatitis B surface antigen (HBsAg), and antibodies to hepatitis B core antigen (HBcAb) and to hepatitis C virus (anti-HCV) were investigated in all patients; antibodies to HBsAg (HBsAb) and IgG antibodies to hepatitis D virus (anti-HDV) in all HBcAb-positive patients; hepatitis B e antigen and antibodies to HBeAg (HBeAg) in all HBsAg-positive patients; IgG antibodies to
hepatitis A
virus (anti-HAV) in the first 307 patients; and IgG antibodies to hepatitis E virus (anti-HEV) in the first 91 patients. As control groups, contemporary voluntary blood donors were studied for prevalence of HAV, HBV, HCV and HEV. The percentages of HBcAb, HBsAg, anti-HCV and anti-HEV (58.5, 14.5, 58.5 and 6.6%, respectively) were significantly higher in anti-HIV-positive patients than in control groups (3.2, 0.5, 1.0 and 1.8%, respectively) (P = 0.000). The prevalence of HBcAb was significantly higher in IVDU (72.6%) than in heterosexuals (33.8%) (P = 0.0001) and in homosexuals (59.6%) (P = 0.0189). The percentage of HBsAg was significantly higher in IVDU (19.2%) than in heterosexuals (6.3%) (P = 0.0004). Anti-HCV was significantly higher in IVDU (92.3%) than in homosexuals (14.1%) and in heterosexuals (33.1%) (P = 0.000 in both cases). The prevalence of anti-HDV was relatively low (1.9%). There was no difference in the percentage of anti-HAV between HIV-positive and negative subjects. In conclusion, there is a high prevalence of HBV and HCV infections in HIV-positive patients from our area. Drug use is the main route of transmission, but prevalence of HCV in patients with, probably, sexually acquired
HIV infection
is also higher than in the control group. The increased prevalence of HEV infection in HIV-positive individuals is another provocative finding that warrants further study.
...
PMID:Prevalence of hepatitis viruses in an anti-human immunodeficiency virus-positive population from Argentina. A multicentre study. 1084 30
The issue addressed below concerns sex differences in consumption patterns and ways of financing the drug habit among intravenous heroin users. The findings are linked to recorded differences in various health indicators. The article is based on data collected through 1,840 interviews with heroin abusers who contacted the "Needle-Exchange Bus" in Oslo during the years 1993-97. Analysis indicates the existence of substantial differences between women and men along a number of variables. Women report injecting more frequently than men and using on average more heroin per injection. Women also finance their drug habit differently, as more than half of them report some income from prostitution. The finding may seem paradoxical as women also appear to have a lower risk of dying from an overdose/poisoning and a lower risk of contracting
hepatitis A
and B than male injecting misusers. The risk of contracting
HIV
and other sexually transmitted diseases, on the other hand, appears to be greater among female injectors.
...
PMID:[Sex differences concerning the habit patterns and health among intravenous heroin addicts in Oslo]. 1085 14
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