Hepatitis C Virus Ebook

Alternative Hepatitis C Treatments


Alternative Hepatitis C Treatments Overview


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Human Immunodeficiency Virus And Viral Hepatitis Infection

The viral infections which are of interest to clinicians, and especially surgeons, are human immunodeficiency virus (HIV) and hepatitis B and C viruses (HBV and HCV). This stems from their transmission risk from patient to healthcare worker or vice versa. Guidelines for reducing the risk of transmission of HIV, HBV and HCV are available for healthcare workers. Their main objective is to minimize exposure of any individual to blood and body secretions regardless of infective status of the second individual involved. Routine serological testing for HIV is not recommended. The debate over testing has not been made easier by the finding that prior knowledge of HIV status does not decrease the risk of transmission. In addition, a negative test does not exclude HIV infection as a seroconversion window exists which may last up to 3 years and during which a person may have circulating antigen but has not yet produced the antibody. If testing is required, consent must be obtained and, if...

Hepatitis A Virus Infection And Immunity

Hepatitis A is an acute, self-limiting infection of the liver, caused by an enterically transmitted picorna-virus. As the virus is not cytolytic, liver cell damage is assumed to be immunologically mediated. While frequently asymptomatic, especially in the young, infection occasionally results in fulminant hepatitis and death. Recovery from the disease is accompanied by lifelong protection against reinfection. Protection is mediated by circulating antibodies and can be passively transferred. Hepatitis A has a relatively short incubation period (15-49 days), is transmitted fecal orally and is followed by long-lasting immunity that can be passively transferred. In 1973, virus-like particles were identified in the feces of volunteers experimentally infected with the MS-1 strain of hepatitis A virus (HAV). These particles were specifically aggregated by convalescent, but not by preinfection, serum. The identification of the etiological agent -and the demonstration that infection could be...

Hepatitis B Virus Infection And Immunity

Hepatitis B virus (HBV) infection is a major public health problem, infecting approximately 300 million people worldwide, and is a major cause of chronic liver disease and hepatocellular carcinoma (HCC). The majority of adults infected have a transient hepatitis from which they completely recover and clear the virus. Rarely the disease becomes fulminant and the patient may die. Between 5 and 10 of adults become persistently infected and develop chronic liver disease. In the majority of cases of vertical transmission the virus is not eliminated and the child becomes chronically infected, greatly increasing its risk of developing cirrhosis and HCC. HBV is a member of the Hepadnaviridae, a related group of hepatotropic, enveloped, double-stranded DNA viruses which have small genomes. The HBV genome is 3.2 kb in size and contains four open reading frames (Figure 1). These encode the envelope (hepatitis B surface antigen, HBsAg), nucleocapsid (hepatitis B core and 'e' antigens, HBcAg and...

Hepatitis C Virus Infection And Immunity

Hepatitis C virus (HCV) was first characterized in 1989, following successful cloning from copy DNA extracted from infectious chimpanzee plasma. The natural route of infection is unknown, but HCV is blood borne, and therefore high-risk groups for infection include intravenous drug users and recipients of unscreened blood and blood products (e.g. hemophiliacs). Sexual transmission does not appear to be a major route of spread of infection. Vertical transmission from carrier mothers is around 2-10 . Estimates of the prevalence of infection vary between 0.1 and 1 of the population of Europe and the USA. There may be significant fluctuations from this in other countries - for example, rates of 15-20 anti-HCV positivity have been reported in Egypt. The majority (possibly 75 ) of HCV infections result in chronic carriage of the virus. The percentage of chronic carriers who will progress to clinically significant liver disease (chronic hepatitis, cirrhosis, hepatocellular carcinoma) is...

Alcoholic Hepatitis and Enteral Nutrition

Seventy-one patients with severe alcoholic hepatitis were randomized to prednisone 40mg day or EN giving 2000kcal day for 28 days and then followed for 1 year or until death. The EN was a branched-chain-enriched diet and patients on steroid therapy were encouraged by dietitians to eat 2000 kcal day with 1 g kg day of protein. No patients from the steroid arm dropped out, whereas 8 35 patients from the EN arm did not receive EN for the entire period but were included in the analysis (intent to treat analysis). It is of interest that all patients in the steroid arm ate 80 of the prescribed diet. Using intent to treat analysis, there were no differences in mortality or complications in the hospital between groups. After discharge, even when confounding variables were adjusted, the EN group had a significantly better survival. Since both groups seemed to receive the same energy intake, the reason for better long-term survival with EN needs further study. Was it because of the use of...

The Amplicor HCV Monitor 20 and Cobas Amplicor HCV Monitor 20 Test Roche Diagnostic Systems

Based on reverse transcription polymerase chain reaction (RT-PCR), the Amplicor HCV Monitor test (Roche Diagnostic Systems) was developed. 5 Recently, an improved version 2.0 was introduced, which achieved an equivalent quantitation of each genotype over the quantitative range (5 x 102 to 5 x 105 copies of RNA mL). 6,7 HCV RNA is extracted from plasma by chaotropic salt and is then precipitated by isopropanol. Both RT and PCR of RNA are accomplished in one tube using the recombinant thermostable DNA polymerase (rTth), which offers both reverse transcriptase activity, forming a cDNA from the RNA target sequence of the 5' UTR, and polymerase activity for amplification of the cDNA under appropriate conditions. An internal quantification standard shows the same primer-binding sites as the target but with a changed internal sequence, which allows binding to special detection probes. This allows quantification after a series of dilutions at the end of the assay. To meet the needs of routine...

Hepatitis E F And G Viruses Infection And Immunity

Michael A Purdy, Hepatitis Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA In the 1970s the development of sensitive and specific serologic assays for markers of acute infection by hepatitis A virus (HAV) and hepatitis B virus (HBV) showed that enterically and parenterally transmitted viral hepatitis, not caused by HAV or HBV, occurred throughout the world. Two of these viruses, HCV and HEV, have been isolated, cloned and sequenced. In the 1980s the development of serologic assays for these viruses indicated that additional enterically and parenterally transmitted hepatitis-associated viruses exist. Research is ongoing to elucidate the immunology, clinical features and pathology associated with these viruses.

Hcv Rna Quantitation

Quantitation of HCV RNA by bDNA technology is possible with the commercial VERSANT HCV RNA 3.0 assay. The performance characteristics of this test were established in our laboratory during the so-called ''beta trials'' before licensing and are given in Table 1. 4 Our findings were essentially confirmed by other studies, 11,12 and showed that the assay, from an analytical point of view, can be used as a routine tool for HCV RNA quantitation in clinical laboratory settings. Table 1 Analytical performance characteristics of VERSANT HCV RNA 3.0 assay Table 1 Analytical performance characteristics of VERSANT HCV RNA 3.0 assay

Hepatitis A

Diagnosis Hepatitis A -Hepatitis A immune globulin, 0.02 mL kg IM (usually requires multiple injections at different sites), when given within 2 weeks after exposure to HAV, is 85 effective in preventing symptomatic infection. -Hepatitis A vaccine (Havrix) if > 2 yrs 0.5 mL IM, repeat in 6-12 months.

Hepatitis E virus

Hepatatis E virus (HEV) is a member of the Calicivir-idae family. Hepatitis E (HE) is a self-limiting disease, similar to hepatitis A, with no known tendency for chronicity. Hepatitis E occurs as large scale epidemics in developing countries, and also as sporadic cases. Outbreaks have been reported and confirmed either serologically or with the reverse transcriptase polymerase chain reaction (RT-PCR) in over 30 countries throughout the world. The primary source of infection is usually drinking water contaminated with water from a sewage system. Person-to-person contact has been noted as a very rare cause of transmission, and in a recent outbreak in India vertical transmission of HEV from infected mothers to infants during the third trimester of pregnancy was noted. Initial reports of HE epidemics failed to find cases of HE in pediatric populations however, the development of diagnostic tests have shown HEV is a common cause of acute hepatitis in this age group. The attack rate is...


Hepatitis is characterized by acute and discrete onset of symptoms and jaundice or elevated serum aminotransferase levels. At present, hepatitis A, B, C, non-A and non-B, and delta are reportable. The laboratory diagnosis of each of the hepatitis viruses is listed below. Hepatitis A. Detection of IgM to the hepatitis A virus (anti-HAV). Hepatitis B. (1) Detection of IgM to hepatitis B core antigen (anti-HBc) or hepatitis B surface antigen (HBsAg) and (2) anti-HAV negative, if done. Hepatitis C. Detection of antibody against hepatitis C antigen (anti-HCV), (2) serum aminotransferase levels greater than 2.5 times the upper limit of normal, (3) anti-HAV negative, if done, and (4) anti-HBc or HBsAg negative, if done. Non-A, non-B hepatitis. (1) Serum aminotransferase levels greater than 2.5 times the upper limit of normal, (2) anti-HAV negative, and (3) anti-HBc and HBsAg negative. Delta hepatitis. (1) HBsAg or anti-HBc positive and (2) detection of antibodies to hepatitis delta virus...

Hepatitis B

Hepatitis B, or serum hepatitis, is spread mainly through contaminated blood, often from unsterilized needles shared by drug users or used for tattoos or ear or body piercing. The virus can also be transmitted sexually. Over 100,000 people are infected yearly in the United States, but this number is decreasing due to the recent introduction of a vaccine. In addition to the initial disease, which is more severe than hepatitis A (more liver damage and fatality rate of 10 ), those infected are at higher risk of liver cancer.

Hepatitis G virus

Recently, a new hepatitis-associated virus, hepatitis G virus (HGV), has been cloned and sequenced. HGV, an RNA virus, is a member of the Flaviviridae family, and is distantly related to HCV. Originally this virus was one of the viruses referred to as HEV. Although HGV has been identified as a hepatitis-associated virus and is associated with acute and chronic hepatitis, research has failed to prove that HGV is hepatotropic. At this time no serologic test exists for detection of HGV-infected individuals, as no HGV antibodies have been detected in infected individuals using either recombinant HGV proteins See also Calicivirus, infection and immunity Hepatitis B virus, infection and immunity Hepatitis A virus, infection and immunity Hepatitis C virus, infection and immunity Togavirus, infection and immunity Viruses, immunity to.

Hepatitis F viruses

Serologic testing has identified five hepatropic viruses HAV, HBV, HCV, HDV and HEV. These viruses account for almost all human viral hepatitis however, a small percentage of patients exhibiting the signs and symptoms of acute viral hepatitis do not have serologic evidence of infection with any of these viruses. Researchers continue to search for the viruses associated with non-ABCDE hepatitis. Many of these enterically and parenterally transmitted viruses have been tentatively designated hepatitis F virus (HEV). However, at this time no single virus has been recognized as being HEV. Some researchers have suggested the non-ABCDE viruses are really one of the known hepatitis viruses and serologic testing has failed to detect the viral-specific antibodies present in infected individuals. Serologic testing of individuals with HCV and HEV infection has shown that the serologic tests available for these viruses do not detect every infected individual. It has also been suggested that a new...

Adenoviruses as vectors for the delivery of foreign genes

Replaced with foreign DNA insertion of the hepatitis B surface antigen (HBsAg) gene in place of the partially deleted Ad E3 results in the expression of HBsAg which elicited an antibody response in hamsters. Recently, many additional foreign genes have been cloned into Ad vectors. Foreign genes have also been placed and expressed in other Ad sites including positions downstream from the Ad major late promoter (MLP). The Ad MLP is a very active transcriptional start site which results in the expression of large amounts of foreign proteins. To elicit higher titers against a given antigen, duplicate cloning of the gene into several serotypes is performed, permitting booster immunizations without augmentation of a serotype-specific anti-Ad-neutralizing antibody response. Since there has been extensive use of the Ad4 and 7 serotypes in young adults in the military, these types are obvious choices for such recombinant vaccines. The efficacy of Ad constructs designed for immunization is...

How is the harm of a treatment documented

Occasionally, drugs may have serious adverse effects such as allergic reactions, hepatitis, cardiac arrhythmias and gastric ulcer. Despite this, attributing an adverse event to a specific treatment can sometimes be difficult, particularly when the event is rare, unexpected, or appears a long time after the start of treatment. It can also be difficult to recognize an adverse effect when it may occur as part of the natural history of the underlying condition. These challenges are discussed in Chapter 4.

Alcohol and Nutrition


Effects of Alcohol on Liver Function


Alcoholic Liver Disease

Alcoholic liver disease is among the top ten causes of mortality in the US with somewhat higher mortality rates in western European countries where wine is considered a dietary staple, and is a leading cause of death in Russia. Among the three stages of alcoholic liver disease, fatty liver is related to the acute effects of alcohol on hepatic lipid metabolism and is completely reversible. By contrast, alcoholic hepatitis usually occurs after a decade or more of chronic drinking, is associated with inflammation of the liver and necrosis of liver cells, and carries about a 40 mortality risk for each hospitalization. Alcoholic cirrhosis represents irreversible scarring of the liver with loss of liver cells, and may be associated with alcoholic hepatitis. The scarring process greatly alters the circulation of blood through the liver and is associated with increased blood pressure in the portal (visceral) circulation and shunting of blood flow away from the liver and through other organs...

Pyridoxine Deficiency

Pyridoxine (vitamin B6) is required for transamination reactions, including the elimination of homo-cysteine. Pyridoxine deficiency in chronic alcoholism is caused by poor diet, whereas displacement of pyridoxal phosphate from circulating albumin by the alcohol metabolite acetaldehyde increases its urinary excretion. Low serum levels of pyridoxal phosphate are common in chronic alcoholics, and pyridoxine deficiency is manifest by peripheral neuropathy and sideroblastic anemia. In alcoholic hepatitis, the serum level of alanine transaminase (ALT) is disproportionately low compared to aspartate

Changing Perspectives On Contaminants

The lines of disease causation have become blurred at the genetic level by the discovery of microbe-induced disease processes not originally associated with microbial causes and only recently identified by genotypic approaches. The latter include viral-induced cancerso (83-85), schizophrenia (86), and diabetes mellitus (87). Borrelia burgdorferi DNA incorporated in the genome of arthritic mice (88) and detected in humans (89) and a list of organisms referenced by Relman (87) have been found using genotypic approaches to detect microbial genes inserted into the genome of man and animals and therefore associated with specific diseases. These include Helicobacter pylori (peptic ulcer disease), hepatitis C virus (non-A, non-B hepatitis), bartonella henselae (Bacillary angiomatosis), Tropheryma whippelii (Whipple's disease), sin nombre virus (Hantavirus pulmonary syndrome), and Kaposi's sarcoma-associated herpes virus (Kaposi sarcoma). In this context Fredricks and Relman have called for...

Epidemiology And Clinical Features

Currently, eight serotypes of human astrovirus are recognized (HuAst 1-8) based upon epitopes on ORF2. It is also possible to genotype HuAst by examination of sequence data of ORF1a, ORF1b, and the 5' end of ORF2, 12 and genotypes equivalent to the eight serotypes have been defined. Recently, evidence for a novel recombinant HuAst has been uncovered. 13 There is no cross-reactivity between the HuAst serotypes, and immunity to one does not give immunity to the others. Astroviruses have been detected in diarrheic animals and as a cause of hepatitis in ducks. Phylogenetic analyses of a large collection of sequences from a variety of astroviruses showed that all the HuAst clustered together separate from the nonhuman strains however, the branching order of the astroviruses was the opposite of their host species indicating the possibility of cross-

Bio Robot Workstations

For the extraction of hepatitis C virus RNA, it was shown that it is possible to achieve a detection level of 12.8 IU mL (95 confidence). Cross-contamination studies have confirmed that the use of the BioRobot 9604 does not pose a detectable contamination risk. 2 For hepatitis B virus detection, Mitsunaga et al. describe that it was possible to quantify DNA in all samples extracted by the BioRobot 9604 which contained more than 500 genome equivalents mL. Extraction of 96 samples could be completed within 2 hr. 3

Assay Formats Direct Hybridization

In addition to expression profiling, sequence-specific hybridization of labeled PCR product to microspheres has been performed. A sensitive multiplexed bead assay for the detection of three viral nucleic acids (HIV, HSV, and HCV) was developed. Here labeled primers were used in the amplification of the relevant viral nucleic acids, which were hybridized to sequence-specific oligonucleotides bound to the beads. 5

The Concept of Infection

A person with a subclinical infection (acute and chronic) looks in full health, and the disease can only be diagnosed by detecting the causative agents, specific antibodies, and functional and morphological changes in the organs and tissues that are specific for a given disease. Such patients (or carriers) are a special danger for the surrounding people since they are the source of infection. At the same time, a repeated subclinical infection in poliomyelitis, diphtheria, influenza, and some other acute infections promotes formation of an immune group of people (herd immunity). Acute and chronic subclinical forms (carrier state) are more common in typhoid fever, paratyphoid B, salmonellosis, viral hepatitis B, etc. Recovery from some infectious diseases, e.g. dysentery, typhoid fever, paratyphoid, diphtheria, meningococcal infection, viral hepatitis B, is not always attended by complete destruction of the microbes in the patient. Carrier state can persist in persons who sustained...

Immune responses of the host

Arenaviruses are generally carried by rodents with little ill-effect to the carrier however, transmission from rodents to primates can cause severe encephalitis, hepatitis or hemorrhagic syndrome. Thus, rodent and humans can have drastically different immunologic and pathologic responses to infection. We will describe the classical studies of cell-mediated immunopathology in the LCMV murine model with the caveat that it does not apply to arenavirus disease in primates. LCMV infection induces inflammatory intermediates such as interferon y (IFNy) and tumor necrosis factor a (TNFa), both of which influence the host's immune response to other pathogens. IFNy stimulates the proliferation of natural killer (NK) cells that serve to eliminate certain pathogen-infected cells and some tumors. TNFa produced in the liver as a result of LCMV infection can clear hepatitis B virus infection, even in perforin-negative mice, probably by inducing an RNase that destroys the hepatitis viral nucleic acid.

Infectious Disease Applications

The development and ongoing improvement of bDNA technology during the past decade was mainly driven by the increasing demand for quantitation of nucleic acids in clinical virology. Understanding the natural history and pathogenesis of chronic viral infections caused, for instance, by hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) has been greatly supported by accurate determinations of viral load. Consequently, measurements of HBV DNA, HCV RNA, and HIV RNA are extensively used in today's clinical practice to monitor the efficacy of antiviral treatment, predict the outcome of therapeutic strategies,

Membranous Glomerulopathy

Membranous Glomerulopathy

Membranous glomerulopathy is a major cause of the nephrotic syndrome in adults (1,2). Only in the past decades has it been surpassed by focal and segmental glomerulosclerosis as the main cause of the nephrotic syndrome (3-5). Membranous glomerulopathy develops mostly idiopathically, but can also be seen in relation with and possibly secondary to, among others, hepatitis B, Sjogren's syndrome, transplantation, lupus erythematosus, diabetes mellitus, sarcoidosis, syphilis, exposure to certain drugs and heavy metals (penicillamine, bucillamine, gold, mercuric chloride), and malignancies (10 ), including carcinomas, carcinoids, sarcomas, lymphoma's, and leukemias (2,6-10). The possibility of a malignancy must be considered especially in older patients with membranous glomerulopathy. In these patients it is also imperative to perform urinary immunoelectropho-resis routinely to rule out myeloma and renal primary amyloidosis (AL) (2). Finally, idiopathic membranous glomerulopathy, of which...

Mitochondrial antigens

Mitochondrial antibodies are detected in 87-98 of patients with primary biliary cirrhosis. They are also observed in 25-28 of patients with active chronic hepatitis and in 25-30 of patients with cryptogenic cirrhosis. They are only seldom observed in patients with extrahepatic biliary tract obstruction and occur very rarely in normal subjects.

Viruses As Causes Of Cancer

Animal viruses can be divided into two broad groups those with DNA genomes and those with RNA genomes. The DNA viruses with oncogenic potential are from six distinct virus groups hepadnaviruses, papillomaviruses, polyomaviruses, herpesviruses, adenoviruses, and poxviruses. Two different families of RNA viruses have been found to have oncogenic potential retroviruses and a flavivirus, hepatitis C virus (Figure 4.1, Table 4.2). Some viruses can act as carcinogens when infecting their natural host, either human or animal. Others, such as adenoviruses or SV40 (a polyomavirus), show their oncogenic potential only in experimental settings, such as infection of cell cultures (Chapter 14). The time it takes different tumor viruses to cause neoplasms can vary widely (Flint et al., 2000). Some induce tumors rapidly, within days or weeks (e.g., the transducing retroviruses), while others take months if not years for cancer development (e.g., human hepatitis B virus). Some tumor viruses, such as...

Medical Infections In Surgical Patients

Nasotracheal intubation and to a lesser degree orotracheal intubation increase the risk of sinusitis. Lumbar puncture and both spinal and epidural anesthesia carry a small risk of meningitis. Instrumentation of the urinary tract increases the risk of cystitis and pyelonephritis. Patients with hemodialysis access or other implantable or temporary central venous access methods are at risk for bacterial endocarditis. Similarly, patients with preexisting valvular heart disease are at risk for seeding of the valves during invasive procedures. Patients receiving antibiotics, even those receiving only a prophylactic dose, are at risk for Clostridium difficile colitis. Patients receiving blood transfusions have a slight risk of hepatitis or HIV exposure, although transmission by transfusion continues to decrease with technological improvements.

Donor Insemination and Egg Donation

Donor insemination is used when sperm are incapable of fertilizing the egg. Usually this occurs if the male produces very little or no sperm. Sometimes, donor sperm is used when the male partner is the carrier of a genetic disorder that could be transmitted to the baby. Sperm donors should be between ages eighteen and fifty-five, and all should be screened for genetic disorders, such as cystic fibrosis, and for various types of chromosomal abnormalities and infectious disease, including hepatitis, syphilis, cytomegalovirus, and HIV. As with the use of intrauterine insemination, the female partner undergoes ovarian stimulation to maximize the number of follicles released during ovulation. Pregnancy rates resulting from the use of donor insemination are between 32 percent and 50 percent after ten inseminations.

Renal Anatomy and Basic Concepts and Methods in Renal Pathology

Most glomerulopathies are immunologically mediated and are the result of antibody-induced injury. This can occur as a consequence of antibody combining with an intrinsic antigen in the glomerulus or antibody combining either in situ or in the circulation with an extrinsic glomerular antigen, with immune complexes localizing or depositing in glomeruli. With circulating immune complexes, the antigens may be of endogenous or exogenous origin. Endogenous antigens occur in diseases such as systemic lupus ery-thematosus and include components of nuclei such as DNA, histones, etc. Exogenous antigens are usually of microorganism origin and include bacterial products, hepatitis B and C viral antigens, malarial antigen, etc. Circulating immune complexes are trapped or lodge in glomeruli in the mesangium and subendothelial aspects of capillary walls. Less commonly, they may be found in subepithelial locations. It is the electron microscope that precisely localizes the deposits. Certain diseases...

Clinical Pictures Seen After Hiv Infection

Hepatitis B and C may cause chronic liver damage and due account should be taken of liver function in those patients known to be carriers or known to have had B or C hepatitis. Hepatitis A does not produce chronic sequelae but may present for surgery during the active or prodromal phases of the disease and again, liver function should be tested and the anaesthetic managed accordingly. The AIDS-related conditions may be of interest to the anaesthetist when the patient presents for surgery but the possibilities are so broad that each must be taken on its merits. Patients with PGL may present for lymph node biopsy. Unfortunately, the majority of people infected with hepatitis B, C and HIV are asymptomatic and not known to the medical community. While precautions against cross infection are usually taken in those patients known, to be infected, it is more logical to take precautions in all patients and assume that every patient is potentially infectious. It is thus, wise for anaesthetists...

TABLE 565 Common Infections after Cardiac Transplantation

Of special note is the risk of CMV infection after cardiac transplantation. CMV is a common virus to which the majority of adults have been exposed, as demonstrated by the presence of anti-CMV IgG antibodies in the serum. Posttransplantation, CMV infections can occur due either to the reactivation of latent virus in a previously infected recipient or the development of a new infection with a different viral strain transmitted with the donor organ. The latter situation is much more serious and potentially life-threatening, particularly in recipients who were CMV-negative prior to transplantation. Routine posttransplant surveillance for CMV infection is performed utilizing serial IgG and IgM antibody testing and throat, urine, and serum buffy coat cultures. The recent development of CMV antigenemia assays has enhanced the early detection of CMV infection. CMV disease can occur in either a mild or severe form. Mild disease is manifested by a flulike illness with low-grade fever, fatigue,...

Rationale For Xenotransplantation

Xenotransplantation has been viewed as a plentiful source of organs and tissues for transplantation (Table 1). 1,2 However, xenotransplantation may even be preferred over allotransplantation in certain circumstances. Where organ failure is caused by a viral infection, e.g., hepatitis, xenotransplantation might be preferred because the transplant would resist reinfection by the virus that caused organ failure. 3 Xenotransplantation might also be preferred as a way of delivering genes of therapeutic importance. For example, an animal source might be genetically engineered to express a gene at a high level or under regulated conditions.

TABLE 613 Dosages and Common Side Effects of Some Drugs Used in Tuberculosis Adults

Preventive therapy with INH should be considered for patients with recent conversion to PPD-positive status, for persons who have been in close contact with an individual with active tuberculosis, for anergic individuals with known tuberculosis contact, or if the prevalence of tuberculosis is 10 percent or higher in the community.16 The decision to institute therapy should be based on the likelihood that the positive PPD reaction represents true exposure to M. tuberculosis, the risk of progression to active disease, and the likelihood of INH-induced hepatitis. Therapy should continue for a minimum of 6 months for adults, 9 months for children, and 1 year for those with immunosuppression or HIV.15 Those at risk for INH hepatotoxicity should be closely monitored for its development if treatment is elected. For those exposed to INH-resistant strains, or those who are intolerant to its use, rifampin and other antimycobacterial agents have been used, but experience is limited.

Personal hygiene practices of consumers

Personal hygiene includes cleanliness of the hands, hair, clothing, and body in general. Hand washing is most frequently the sentinel behavior for assessment of personal hygiene in consumer food safety studies. From a Hazard Analysis and Critical Control Point (HACCP) perspective, the critical control point for ensuring the safety of foods that are prepared to be served without heating is personal hygiene. Controlling the transfer of pathogens from the hands to food is important for almost all foodborne illnesses, but especially (1) raw vegetables and fruits (2) some types of desserts (3) raw or undercooked foods exposed to polluted water and (4) previously cooked foods handled by consumers and served without additional heating. It is estimated that 5 of Hepatitis A cases are foodborne, 20 of Shigella cases, and 40 of Norovirus cases are estimated as being foodborne (Mead et al., 1999). Thus, hands contaminated with fecal pathogens can be the source of pathogens in foods (Feachem,...

Reverse Transcription and the Human Genome

When reverse transcriptase was first described, it was believed to be a peculiarity of retroviruses. However, researchers now know that reverse transcription also occurs during the replication of the DNA virus hepatitis B, and that RNA-copying DNA polymerases function within human cells. One of these host reverse transcriptases is telomerase, an enzyme that helps maintain chromosome ends.

Humanmouse hematopoietic chimeras

Recently, Lubin and colleagues described a new approach enabling engraftment of human PBMC in normal strains of mice and rats, following split-dose lethal irradiation. Irradiated animals are initially converted into SCID-like animals by means of bone marrow transplantation from SCID donors and subsequently are infused with human PBMC. These chimeric animals allow an effective and rapid engraftment of human cells, enabling their functional study early after transplant. Moreover, a marked human primary and secondary humoral response, as well as vigorous antiallogeneic human cytotoxic T lymphocyte (CTL) response, could be generated in the human-BALB c radiation chimera by immunizing them with foreign antigens and allogeneic cells, respectively. In addition, the marked immunodeficiency induced in these radiation chimera has recently enabled us to transplant human liver fragments under the kidney capsule in such mice and to induce hepatitis C viremia, so as to provide a new murine model...

General features of CAH

Chronic hepatitis ranges from an asymptomatic disease recognized only by biochemical abnormalities to one that is severe and progressively cirrhotogenic. Some cases of autoimmune hepatitis can have a long asymptomatic preclinical course, as pertains for other autoimmune disorders. Likewise, an insidious onset and clinical latency is usual for CAH associated with infection with HCV and, in many instances, with HBV. Cases of chronic active hepatitis will have some common general features related to liver dysfunction or cirrhosis, whatever the cause, and other features related to the individual etiological agent or process. The general features include symptoms of hepatitis, including nausea, anorexia, jaundice, hepato-splenomegaly, and biochemical evidence of liver parenchymal damage, in particular high levels of transminase enzymes in serum. The biopsy of the liver may show either of two histological lesions, named as chronic persistent hepatitis which is indolent and nondestructive,...

Liverspecific autoantigen

A liver-specific autoantigen as the target for immune-mediated damage in autoimmune hepatitis has not yet been identified. Crude preparations of liver cells and liver cell membrane preparations have been examined in various ways for reactivity with serum or peripheral blood T cells from patients with autoimmune hepatitis with promising but not unequivocal results. No liver-specific autoantigen has yet been identified by techniques applied successfully in other autoimmune disease, namely immunoblotting on electrophoreticaily separated liver cell membrane preparations, or probing gene expression libraries, using serum from cases of autoimmune hepatitis. Claims for ASGP-R as a liver-specific autoantigen relevant to autoimmune hepatitis need more substantiation.

Mechanisms of hepatocellular damage

The mechanisms of hepatocellular damage in chronic active hepatitis will vary according to the particular cause. In CAH-B there are two likely processes, a specific immune deficiency to critical antigens of the virus, probably the surface antigen, that allows a state of tolerated infection to occur, and a nonelimin-ative attack by cytotoxic T cells on epitopes of the core antigen (HBcAg) expressed with class I major histocompatibility complex (MHC) molecules on the liver cell membrane. In CAH-C, the cytotoxic T cell attack would be on epitopes of HCV expressed with class I MHC molecules on the liver cell membrane. In autoimmune hepatitis the suspected but as yet unknown processes include a T cell-dependent cytotoxicity due to cytokines released from CD4 T cells or cytotoxic effects of CDS T cells, and an immuno-regulatory failure permitting responses to tolerated hepatocellular autoantigens. Whether any pathogenetic connotations can be ascribed to the serologic reactivities, ANA, SMA,...

A final common immunocytotoxic pathway in CAH

The occurrence of autoantibody to various liver cell constituents, together with histological appearances of CAH in diseases that are not primarily attributable to an autoimmune process, has led to the idea that an immune-mediated attack on liver cells can supervene as a 'final common immunocytotoxic pathway' in liver diseases with different initiating causes. Whilst this may indeed occur, the features of this postulated 'secondary' autoimmune hepatitis do not really simulate those of the primary disease. Accordingly it is recommended that autoimmune hepatitis be regarded as an entity sui generis for which the nature should be better understood if and when a disease-specific and tissue (liver)-specific autoantigen is identifiable.

Structure and Function

Some RNA viruses, such as the hepatitis delta virus, also include a ribozyme as part of their inherited RNA molecule. During replication of the viral RNA, long strands containing repeats of the RNA genome (viral genetic information) are synthesized. The ribozyme then cleaves the long multimeric molecules into pieces that contain one genome copy, and fits that RNA piece into a virus particle.

Differential Diagnosis

The differential diagnosis of biliary colic includes other conditions associated with upper abdominal pain, including gastritis, gastroesophagal reflux, pancreatitis, hepatitis, and peptic ulcer disease. Atypical myocardial infarction should be considered in older patients. Acute renal colic can be associated with upper abdominal and upper back pain. Both conditions can also be associated with flank tenderness, nausea, and vomiting. Renal colic does not have a circadian rhythm, and the pain is colicky, not continuous, as in biliary colic. Nonetheless, it can be difficult to distinguish biliary from renal colic, and definitive imaging studies may be needed to make the correct diagnosis. Acute pyelonephritis, like cholecystitis, can be associated with flank and upper quadrant pain, but pyuria confirms the former diagnosis. Appendicitis can sometimes be associated with RUQ pain, especially in pregnancy or in patients with a retrocecal or redundant appendix. In women of childbearing age,...

Clinical Features

Clinical presentation of acute liver disease is variable. Symptoms of hepatocellular necrosis accompanying viral hepatitis include anorexia, nausea, vomiting, and low-grade fever. Cholestatic disease is accompanied by jaundice of varying degree, pruritus, clay-colored stools, and dark urine. Biliary colic implies acute obstructive cholestasis of extrahepatic or mechanical etiology, as in common duct gallstones or rapidly growing tumors. Cholestasis resulting from intrahepatic processes and infiltrative disease presents more insidiously with the slow development of jaundice and few other constitutional complaints. Physical findings of acute hepatitis are often limited to moderate enlargement of the liver and tenderness. Chronic liver disease is accompanied by a host of physical findings, including sallow complexion, appendicular wasting, palmar erythema, distinctive cutaneous spider nevi, parotid gland enlargement, and testicular atrophy and gynecomastia in males. Ihe liver may be...

TABLE 824 Differential Diagnosis of Hyperbilirubinemias

Generalizations may benefit the emergency practitioner. A degree of unconjugated hyperbilirubinemia accompanies all hepatocellular diseases, but primary elevations in unconjugated bilirubin are rare and mostly limited to the infant pediatric population, as in neonatal jaundice and Crigler-Najjar syndrome. In the absence of severe underlying or concomitant liver disease, hemolysis does not result in jaundice. Jaundice presenting in the acutely ill and febrile patient will reflect either viral hepatitis or bacterial cholangitis a distinction may be made by noting that cholangitis is usually accompanied by much greater elevations in alkaline phosphatase. The subacute presentation of jaundice in the patient without a history of chronic liver disease is most likely the result of infiltrative disease or slowly obstructing extrahepatic tumor, as in the head of the pancreas.15 6

Chapter References

Centers for Disease Control and Prevention Hepatitis home page 3. Bondesson JD, Saperston AR Hepatitis. Emerg Med Clin North Am 14(4) 695, 1996. 4. Alter MJ, Margolis HS Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 47(RR-19) 1, 1998. 5. Gross JB Jr Clinician's guide to hepatitis C. Mayo Clin Proc 73(4) 355, 1998. 6. Lee WM Medical progress Hepatitis B virus infection. N Engl J Med 337(24) 1733, 1997. 7. Koff R Hepatitis A. Lancet 351(9116) 1643, 1998. 9. Krawitt EL Medical progress Autoimmune hepatitis. N Engl J Med 334(14) 897, 1996.

Biliary Complications

After 12 months, stricture and or obstruction account for the vast majority of biliary complications. Development of a biliary complication is heralded by three typical presentations. Most common is intermittent episodes of fever and fluctuating liver function tests. The second presentation is gradual asymptomatic worsening of liver function tests. Finally, biliary complication may present as acute bacterial cholangitis with fever, chills, abdominal pain, jaundice, and bacteremia. Stricture or narrowing of the bile duct frequently develops insidiously. 7 The presentation of biliary complication can be difficult to distinguish clinically from rejection, HAT, CMV infection, or a recurrence of a preexisting disease (especially hepatitis).

Complications Of Immunosuppressive Agents

Azathioprine interferes with both B- and T-cell responses to antigenic stimulation. Generalized myelosuppression is a common side effect resulting in leukopenia and, to varying degrees, thrombocytopenia and anemia (megaloblastic) and is generally seen within the first few weeks. Other observed toxicities include hepatitis, cholestasis, hepatic vein thrombosis, pancreatitis, dermatitis, and alopecia. Prolonged use also predisposes to malignancies such as squamous cell carcinoma of the skin and lip, cervical carcinoma, and lymphoproliferative disorder.

Analytical epidemiology

In an experimental or interventional study, individuals are randomly allocated to be included in a study group, which is exposed to a factor under study or allocated to a non-exposed control group. Such studies offer the most direct and conclusive method of establishing a causal relationship between a risk factor and a cancer. Although the introduction of a suspected risk factor may happen opportunistically, as in irradiation following the atomic bombs in Japan, the introduction of harmful measures (or withdrawal of beneficial ones) from random sections of the population is not ethical. Although this study design is standard for assessing the effects of treatment, it is applicable only to epidemiological studies of primary or secondary prevention for example vaccination against hepatitis B or screening for breast cancer. Such large and expensive population studies will become more frequent as chemoprevention becomes a reality.

Plants as Bioreactors


Other Complications

Chronic liver disease is an important cause of morbidity and mortality for renal transplant patients. 23 Causes of hepatic dysfunction include (1) viral hepatitis (CMV is leading cause, followed by hepatitis C and B) and (2) antirejection drugs (both azathioprine and CYA cause cholestatic jaundice).

Patents and the Rise of Biotechnology Companies

Among the new companies to take advantage of the court ruling was the Chiron corporation, which cloned the protein that formed the outer coat of the human hepatitis B virus. This protein, which could now be produced without the virus that it normally enclosed, provided the material for the development of the first human vaccine using recombinant DNA technology. The hepatitis vaccine has been available since 1987.

TABLE 1013 Criteria for Hypertension Preeclampsia and Eclampsia

The HELLP syndrome (an acronym for hemolysis, elevated liver enzymes, and low platelets) is an important clinical variant of preeclampsia that has a predilection for the multigravid patient, in contrast to the primigravida, in whom preeclampsia is more common. In the HELLP syndrome, the blood pressure is variable and may not be elevated initially. This fact, combined with the usual complaint of epigastric or right upper quadrant pain, makes it easy to mistake the HELLP syndrome for other causes of abdominal pain, such as gastroenteritis, hepatitis, pancreatitis, or pyelonephritis. The HELLP syndrome should be considered in any pregnant or postpartum patient who presents to the emergency department with a chief complaint of abdominal pain. The diagnosis can be made based on clinical findings coupled with laboratory results (Table 1.0.1.-4).

TABLE 1045 Treatment of Genital Herpes

The safety of acyclovir and valacyclovir during pregnancy has not been established. In pregnant patients with life-threatening disease, such as encephalitis, pneumonitis, or hepatitis, intravenous acyclovir should be used. It should not be used for recurrent episodes or as suppressive therapy. Pregnant women treated with the drug should be reported to the Glaxo-Wellcome registry, which is kept in cooperation with the CDC (1-800-722-9292, extension 38465). Current registry findings do not indicate an increased risk for major birth defects after acyclovir treatment.2,3., 2

Gammaglobulin for prophylaxis and disease prevention

The use of intramuscular gammaglobulin as a prophylaxis against infectious disease in persons exposed to hepatitis A ha established therapeutic benefit. Intramuscular immunoglobulin is also recommended for nonimmune women exposed to rubella in early pregnancy, and for infants or immunosuppressed persons exposed to measles. Specific high-titered preparations of gammaglobulin are also available for prevention of disease following exposure to chicken pox (for immunosuppressed individuals) or following suspected inoculation with rabies virus or tetanus organisms.

Safety of gammaglobulin

A major concern surrounding the infusion of blood and blood products is the potential for the transmission of viruses. Although there was previously a risk of infection with hepatitis C for patients who received factor VIII and factor IX concentrates, human immunoglobulin concentrates have not historically been noted for the transmission of hepatitis. However, there have been a few cases of hepatitis on record that were traceable to injections of intramuscular immunoglobulins, and there have also been instances of outbreaks of hepatitis C in patients who received intravenous immunoglobulins. Most recently, intravenous immunoglobulin concentrates of one manufacturer produced hepatitis C in more than 100 patients in the USA in 1993-1994, with a number of affected individuals also being reported in other countries. Since in each case the starting immunoglobulin is the same as for intramuscular immunoglobulin, it has remained a mystery how intravenous immunoglobulin could acquire...

How safe is blood transfusions

In the UK, most of the information about the safety of blood transfusions comes from the Serious Hazards of Transfusion (SHOT) scheme, which is a national reporting system for serious complications of blood transfusion. The Sixth Annual Report was published in July 2003. Data from SHOT provides great evidence about the risks of transfusions. In the UK each donated unit of blood is tested for HIV, Hepatitis B and C, syphilis, and red blood cell typing for ABO and RH(D) antigens is performed. A donated unit of blood can either be transfused whole (e.g. for babies) or split into several components that can be transfused to different patients. A request for group and save results in the patient's blood being typed for ABO and RH(A) antigens, and the plasma being tested for antibodies that could lyse red cells at 37 C. A request for a blood product results in a full cross-match between the patient's blood and the unit of blood product to be transfused (Fig. 11.12).

Dual Fractal Analysis

Kyono et al (1998) have used the scintillation proximity assay (SPA) to detect hepatitis C virus helicase activity. These authors indicate that hepatitis C virus (HCV) is a major etiologic agent of non-A and non-B viral hepatitis (Choo et al, 1989 Kuo et al., 1989). Kyono et al indicate that at the C-terminal two-thirds of the nonstructural protein 3 (NS3) of hepatitis C virus possesses RNA helicase activity. This enzyme is expected to be one of the target molecules of anti-HCV drugs. The authors utilized the SPA system to detect the helicase activity of NS3 protein purified by an immunoaffinity column. A polyclonal antibody to HCV was adsorbed on the immunoaffinity column. Figure 6.18 shows the curves obtained using Eqs. (6.2a) and (6.2b) for the time course of helicase activity by purified HCV NS3 protein. Note that in this case a dual-fractal analysis is required to provide a reasonable fit. Table 6.7 shows the values of the binding rate coefficient, k, and the fractal dimension,...

Transfusiontransmitted infections

The chance of receiving an infected unit from a British donor is now as low as 1 in 30 million for hepatitis C, 1 in 8 million for HIV and 1 in 260 000 for hepatitis B. Since 1995 only 16 cases of viral transmission was reported to SHOT, and no confirmed transmissions have been reported in the last 2 years. Reduction of the risk depends on exclusion of donors with lifestyle markers indicating a high risk for viral infection and serological testing (PCR-based detection of viral nucleic acid).

Characteristics of the organism and its antigens

HCV is an enveloped virus containing a single-stranded positive-sense RNA genome of 9.4-9.5 kb. It is classified as a separate genus within the family Flaviviridae. The genome includes a 5' nontranslated (noncoding) region (5'NCR) of 329-341 nucleotides, followed by a large single open reading frame cellulose strips. The presence of the relatively conserved core and NS3 gene products are essential to avoid false-negative reactivity arising through failure of antibodies raised against one viral genotype to recognize antigens derived from a different genotype. In contrast, the genetic diversity of the NS4 gene is reflected in sufficient antigenic differences between genotypes to allow synthesis of type-specific NS4-derived peptides for use in serotyping assays. Genome detection assays, such as the reverse transcriptase polymerase chain reaction (RT-PCR) using primers from the highly conserved 5'NCR, are useful for determination of carrier status in anti-HCV-posi-tive individuals....

Evasive strategies by the organism

The majority of HCV-infected individuals become chronic carriers of the virus, even though they possess easily demonstrable, broad-ranging humoral and cellular immune responses. A number of hypotheses have been advanced to explain the failure of these responses to eliminate virus. Both low- and high-density HCV virions may be found in human sera, the multiple densities reflecting association of virus with various lipoproteins and or antibody. The ability of HCV to associate with very low-density lipoproteins, thereby rendering a major proportion of infectious virus nonneutralizable, may be of importance for virus persistence. The existence of HCV as a quasispecies (i.e. a population of viruses each with slightly different sequences) may allow the virus to escape immune surveillance by changing its antigenic determinants. The hypervariable region of E2 shows considerably less genetic divergence in chronically infected patients who are agammaglobulinemia as compared with immunocompetent...

Management Of Hbvinfected Patients

No molecular biology-based assays are necessary for the diagnosis of acute hepatitis B, which is based on serological testing. Chronic hepatitis B is defined by HBsAg persistence in serum for more than 6 months. In this setting, HBV DNA detection-quantification is necessary to determine whether or not HBV is replicating. In the presence of HBeAg, the diagnosis of replicating chronic hepatitis B can be made whatever the viral load. Chronic hepatitis due to precore HBV mutants presents as hepatitis B e antigen (HBeAg)-negative chronic hepatitis B with generally lower replication levels than HBeAg-positive patients. HBeAg-negative chronic hepatitis B (CHB) represents a late phase in the natural course of chronic HBV infection that develops after HBeAg loss and seroconversion to anti-HBe. It is usually associated with mutations in the precore region of the HBV C gene inducing a stop codon that inhibits the production of HBeAg. 11 The diagnosis of HBeAg-negative CHB is based on HBsAg...

Estimation Of Infectivity

Another important reason for HBV viral load determination is the assessment of the infectivity of hepatitis B carriers. Without intervention, more than 90 of HBeAg-positive female chronic HBV carriers transmit the virus to their infants 17 of these, 85-90 develop chronic HBV infection in most cases asymptomatic themselves, thus perpetuating the infection in high-endemicity settings. Immediate postpartum immunization of the infant can efficiently prevent transmission. It has to be considered that the level of viremia present in maternal serum can only be approximated with the HBeAg assay. Recent quantitative evaluation of sera for HBV DNA using molecular hybridization technology has shown that wide fluctuations in the concentration of virus exist in HBeAg-positive carriers. Vertical transmission is rarely documented with maternal HBV DNA levels below 107 geq mL (5 pg mL). 18,19 In a recent study, no cases of trans-placental transmission of HBV were observed with maternal HBV DNA levels...

Prevention of Bacterial Food Poisoning

All foods entering the kitchen should be considered to be potentially hazardous. In any investigation, it is important not to assume that a food cannot be the cause just because it is unlikely or not known to have caused FP in the past. Salads and other vegetables or fruit eaten raw may be contaminated, and outbreaks have been caused by lettuce (S. sonnei and E. coli VTEC 0157), raspberries and strawberries (Cyclospora cayetanensis and hepatitis A), alfalfa sprouts (S. enteritidis), and radish sprouts grown hydroponically (E. coli VTEC 0157). Some of these foods were contaminated at the source by water or sewage, others during processing by infected food handlers (NLV and hepatitis A), and others by food handlers during preparation. It is difficult to avoid or prevent such infections in the kitchen short of cooking everything, and more stringent codes for hygiene at the growing farms and processing plants are required. Cooking food, especially meat, thoroughly will destroy vegetative...

The HIV vaccine challenge

An alternative strategy is the subunit vaccine which has already proved successful for viruses such as hepatitis B. In this respect the advent of recombinant DNA technology has allowed vaccine development to enter a new era. Individual virus genes can now be cloned and expressed in prokaryotic and eukaryotic cells to yield enough antigen for subsequent purification and use in vaccine studies. The viral proteins most likely to be exploited as compound candidate vaccines are those of Env and Gag. Antibodies directed against gpl20 can neutralize HIV in vitro, while Gag protein has been shown to have epitopes recognized by both helper and cytotoxic T lymphocytes.

Symptom Specific Therapy

Since Strep. pneumoniae and H. influenzae are the primary bacterial pathogens of SCD, patients should be vaccinated in childhood against them as well as receiving the hepatitis B vaccine. Parenteral antibiotic therapy usually begins with cephalosporins (i.e., cefuroxime or ceftriaxone), which have excellent activity against these two pathogens. Choice of intravenous antibiotic depends upon the given clinical scenario and culture results.

Pathology and dysfunction

The previous paragraphs stressed the normal anatomy and function, and touched on the problems one might encounter with hepatobiliary disease. The systematic review of all liver diseases is beyond the scope of this chapter however, our focus will be on surgical pathologic states and the most commonly encountered problems on clinical rotations. What soon will be apparent is that many diseases converge in common pathways. Infectious diseases such as hepatitis B and C lead to hepatocytes damage and subsequent destruction of the liver architecture. Cholestasis as a result of obstructing stone disease, but also secondary to tumors, autoimmune disease or cystic disease leads to destruction of hepatocytes and liver architecture as well. With the loss of normal hepatic architecture and function, characteristic signs of liver failure surface can easily be understood based on the anatomy and function as discussed previously. For the sake of this chapter, we will divide liver disease in four...

Problems Of The Liver

Jaundice Hepatitis The most common disease of liver dysfunction is jaundice, characterized by a yellow discoloration of the sk n, nails, eyes, mucous membranes and excretions. Other symptoms include nausea, vomiting, loss of appetite and extreme fatigue. Jaundice is usually caused either by a viral infection of the liver (viral hepatitis) or an obstruction to the flow of bile.

Immunizations of HIVInfected Patients

Ta.b eJ.39z8 summarizes the CDC recommendations for common immunizations. Pneumococcal vaccine is recommended for all patients over 2 years of age. Tetanus-diphtheria vaccine is recommended as a booster every 10 years for those who have completed primary series. The measles-mumps-rubella vaccine is contraindicated because measles is a live vaccine with reported serious reactions in HIV-infected patients. Hepatitis B vaccine is recommended for all high-risk individuals, including injected drug users, sexually active homosexual men, and sexually active men and women with sexually transmitted diseases or more than one sexual partner in the past 6 months. Patients should be referred to a primary care provider for routine immunization.

Gastrointestinal Tract

Microsporidium is an obligate intracellular protozoan that is becoming more commonly recognized as a pathogen in patients with AIDS and the immunocompetent. Most patients present with diarrhea and a wasting syndrome, but hepatitis, peritonitis, and keratitis have been described. Diagnosis by stool examination is difficult due to the small spore size. Immunologic detection of spores with polyclonal serum has been attempted. Definitive diagnosis usually requires intestinal biopsy and detection with transmission electron microscopy. Treatment is difficult. Patients who do not respond to standard antidiarrheal therapy can be tried on octreotide, albendazole, or metronidazole.

Detecting immune complexes in bodily fluids and tissues

Figure 2 Analysis of immune complex composition and specificity. The purified immune complexes are now ready for further analysis, e.g. for separation and examination of antigen and or antibody. An easier procedure for purifying immune complexes is by cryoprecipitation but only a few immune complexes (e.g. a portion of complexes with hepatitis C infection) have the property of precipitating in the cold.

Clinical aspects in human medicine

Immune complexes are found in the circulation and or other biological fluids of patients with a large spectrum of diseases not resembling each other, such as autoimmune, infectious and neoplastic disorders. This proves that elimination of antigens in the stage of immune complexes is a common feature to many diseases, and symptoms may nor necessarily result from their presence. In fact, in many circumstances, it is not possible to differentiate between a role for immune complexes in physiological antigen removal and a deleterious pathogenic factor. In glomerulonephritis the pathogenic role of immune complexes is generally accepted. The following immune complex diseases are frequently associated with nephritis SLE, polyarteritis, cryoglobulinemia and many microbial diseases such as bacterial endocarditis, leprosy, malaria, trypanosomiasis, hepatitis B and C infection and dengue hemorrhagic fever. In contrast, RA, polymyositis, dermatomyositis, cutaneous vasculitis, fibrosing alveolitis...

Clinical Description of Infection

HHV-6B is the principle cause of the exanthem roseola infantum (exanthem subitum), an illness characterized by high fever and development of a rash after fever resolves. 8 HHV-7 can also cause roseola. However, the majority of children with HHV-6B or HHV-7 infection develop an undifferentiated fever, but this may be complicated in some by febrile convulsions, encephalopathy, and hepatitis. Primary infection is rare in adults but can occur including an infectious mononucleosis-type illness. Interactions between HIV-1 and HHV-6A, HHV-6B, or HHV-7 replication occur. Each of the herpesviruses can up-regulate or down-regulate HIV-1 replication under specific conditions, but the significance is uncertain. HHV-6 infection in the first year of life has been associated with more rapid HIV-1 disease progression in vertically infected infants. HHV-6A may contribute to the switch between CCR5 (M-tropic) and CXCR4 (T-tropic) virus late in HIV-1 infection. Reactivation of HHV-6A, HHV-6B, or HHV-7...

Inpatient Therapy Regimen A

Antituberculosis medications have inherent toxicities and side effects INH (hepatitis, peripheral neuropathy), rifampin (hepatotoxicity, flu-like syndrome, discoloration of body fluids staining of contact lenses), PZA (arthralgias, hyperuricemia, hepatitis), ethambutol (optic neuritis), and streptomycin (ototoxicity). Close monitoring is essential.

Other Keratin Disorders

Recent studies have revealed that mutations in keratins expressed in simple epithelia may be involved in the pathogenesis of a number of gastrointestinal diseases. 20 Cryptogenic cirrhosis is a diagnosis of exclusion applicable to an individual with cirrhosis who does not carry a hepatitis B or C virus who does not test positive for serological markers associated with autoimmune hepatitis or primary biliary cirrhosis who has normal iron, ceruloplasmin, and aj-antitrypsin levels and who has no history of alcohol or toxin ingestion. Recurrent mutations in human K8 K18 genes have been shown to predispose individuals to cryptogenic cirrhosis, chronic pancreatitis, and inflammatory bowel disease. 20,34,35 How K8 K18 mutations cause liver disease is still a matter of debate. Animals deficient in K8 K18 are highly susceptible to proapoptotic signals, suggesting that keratins may play a cytoprotective role in the gastrointestinal tract. 20

Vaccination therapies

Are expressed in a lineage-related manner and are also detected in normal tissue (e.g., MAGE, BAGE, GAGE, NY-ESO-1, SSX) 2) tumor-restricted antigens, which are expressed only on cancer cells (e.g., Melan A MART-1, tyrosinase, gp100, CEA, NY-BR-1, rab 38) 3) unique tumor restricted antigens, including point mutations of normal tumor antigens (e.g., P-catenin, MUM-1, CDK-4, p53, ras) 4) overexpressed antigens of normal tissue (e.g., HER-2 neu, p53, MUC-1) and 5) viral antigens (e.g., human papillomavirus, hepatitis B virus, Epstein-Barr virus).

Environmental factors

Mucosal disease virus causes IDDM in cattle. When neonatal golden Syrian hamsters are infected with 3 cell-passaged rubella virus they develop diabetes. 3 cell-specific expression of endogenous retrovirus is associated with the development of insulitis and diabetes in NOD mice. It was also demonstrated that reovirus causes autoimmune IDDM in mice. Transgenic mice expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp), or influenza virus hemagglutinin in the 3 cells have been developed in order to investigate the potential association between viruses and IDDM. Young hosts that express LCMV glycoprotein in their 3 cells develop diabetes when they are exposed to the same virus later in life. Transgenic mice that express influenza virus hemagglutinin in their 3 cells develop autoimmune diabetes. In contrast to the induction of diabetes, LCMV and mouse hepatitis virus (MHV) prevents the development of autoimmune IDDM in the BB rat and the NOD mouse.

Fulminant Hepatic Failure

NAC also appears to be beneficial in the treatment of acetaminophen-induced fulminant hepatic failure. When compared with controls, NAC therapy was associated with increased survival (48 vs 20 percent), decreased cerebral edema (40 vs 68 percent), and decreased vasopressor requirements (40 vs 80 percent). 12 NAC appears to be beneficial in the treatment of other forms of hepatic failure, too, including viral hepatitis and alcoholic cirrhosis. 16

As Comprehensive Gene Expression Profiling

The clinical challenges mentioned above point to a need to understand in a comprehensive fashion the underlying molecular mechanisms of kidney cancers. One recent biomedical breakthrough is the use of high-throughput microarray technology, which allows comprehensive gene expression profiling of tumors. These gene expression profiles can serve as the molecular signatures of particular tumors, and they may be used to distinguish among histological subtypes and novel distinct subtypes that are correlated with clinical outcome. This distinction may reflect the heterogeneity in transformation mechanisms, cell types, or aggressiveness among tumors. For example, approx 100 genes were identified as differentially expressed by serous as compared to mucinous ovarian cancers (27). Other studies have identified distinct gene sets that distinguish between acute myeloid leukemia and acute lymphoblastic leukemias (28), between hereditary breast cancer with BRCA1 and BRCA2 mutations (29), and between...

Hostparasite relationships

Naturally infected Atlantic salmon with systemic disease may have dermatitis, with whitish discoloration of the peduncle and caudal fins. Infected post-smolts have whitish granulomatous nodules, which contain many flagellates, in the pale liver and kidneys. The most severe lesions are in large fish (4-5 kg), with additional brown abscesses in the caudal muscles. Livers and kidneys have multifocal necrosis, with oedema, congestions, haemorrhages and fibrosis. Fish with advanced disease have severe muscular degeneration, cholangio-hepatitis and perihepatitis, encephalitis and meningitis (Poppe et al., 1992). In experimentally infected Atlantic salmon, S. bark-hanus causes disease with high mortality. The clinical signs include skin blisters, ulcers on the body surface (Fig. 3.4) and unilateral exophthalmia (Fig. 3.5). Gross pathologies include haemorrhaging in internal

Hypersensitivity Reactions

Hypersensitivity reactions usually occur within 1 to 6 weeks of beginning phenytoin therapy and can include fever, systemic lupus erythematosus, erythema multiforme, toxic epidermal neurolysis, Stevens-Johnson syndrome, hepatitis, rhabdomyolysis, acute interstitial pneumonitis, lymphadenopathy, leukopenia, disseminated intravascular coagulation, and renal failure. One should always ask about a history of previous hypersensitivity reactions before deciding to restart phenytoin in the emergency department setting.

Coronary Artery Regions

Coronary Arter Bulls Eye

Pseudo-dyskinesis in 54-yr-old male with end-stage liver disease. Left ventricular walls in this 54-yr-old male with end-stage cirrhosis owing to chronic alcohol use and hepatitis C virus infection was normal during diastole (A-C). Apparent hypokinesis dyskinesis in the postero-inferior walls (B,D, arrows) was a result of external pressure from tense ascites secondary to his end-stage liver disease. (Please see companion DVD for corresponding video.)

Penicillins Cephalosporinsb Lactams

The penicillins and cephalosporins are among the most widely used antimicrobial agents. They share a common b-lactam ring and are bactericidal through inhibition of bacterial cell wall synthesis. Potential adverse effects associated with therapeutic use of penicillin and b lactams include hypersensitivity reactions, central nervous system (CNS) disturbances, impaired hemostasis, interstitial nephritis, and hepatitis.

Antimycobacterial Drugs

INH In addition to treating active TB, INH is also used for chemoprophylaxis in patients with positive PPD tests. INH has important adverse effects, including hepatic toxicity and neurotoxicity, at therapeutic doses. Approximately 10 to 20 percent of patients who use INH for chemoprophylaxis will have elevation in serum transaminases and 1 percent will develop overt hepatitis.16 Patients should have the serum transaminase level evaluated frequently, and therapy should be terminated if the level is elevated two to three times above normal.

Stephen L Zawistowski Metamorphosis See Animal Presence Mice

Mice are also used in the development, preparation, and safety testing of vaccines. Mice played a central role in the development of whooping cough and yellow fever vaccines. Experimental vaccines are under development for human hepatitis A, sickle-cell anemia, and malaria. Approaches are being explored with vaccines for treating cancer and producing contraception.

Commercial Application

Transgenic microbes have many commercial and practical applications, including the production of mammalian products. A company called Genentech was among the earliest and most successful commercial enterprises to use genetically engineered bacteria to produce human proteins. Their first product was human insulin produced by genetically engineered Escherichia coli. A variety of other human hormones, blood proteins, and immune modulators are now produced in a similar fashion, in addition to vaccines for such infectious agents as hepatitis B virus and measles.

[2 Phenotype Changes of Fut8 Knockout Mouse Core Fucosylation Is Crucial for the Function of Growth Factor Receptors

Core Fucosylation

GDP-l-Fuc N-acetyl- -d-glucosaminide a1,6-fucosyltransferase (Fut8, E.C. catalyzes the transfer of a fucose residue from GDP-fucose to position 6 of the innermost GlcNAc residue of hybrid and complex types of N-linked oligosaccharides on glycoproteins to form core fucosylation in mammals, as shown in Fig.1A. Fut8 is the only core FucT in mammals, but there are core a1,3-Fuc residues in plants, insects, and probably other species. The Fut8 gene is expressed in most rat organs with a relatively high level expression in brain and small intestine (Miyoshi et al., 1997). a1,6-Fucosylated glycoproteins are widely distributed in mammalian tissues and are altered under some pathological conditions. For example, the level of core fucosylation is elevated in both liver and serum during the process of hepatocarcinogenesis (Hutchinson et al., 1991). The presence of core fucosylation of a-fetoprotein, a well-known tumor marker for hepatocellular carcinoma (HCC), is known to distinguish...

Classification of Infectious Diseases

Hepatitis, brucellosis, etc.), it can also be withdrawn through various organs of the body, e. g. the kidneys, lungs, the mammary glands. The anthroponoses include typhoid fever, paratyphoid, bacterial and amoebic dysentery, cholera, viral hepatitis A, poliomyelitis, helminthiasis (without the second host). The zoonoses include brucellosis, leptospirosis, salmonellosis, botulism, etc.

Diagnostic studies

A diagnosis of cervicitis, typically due to Neisseria gonorrhoeae or Chlamydia trachomatis, must always be considered in women with purulent vaginal discharge. The presence of high-risk behavior or any sexually transmitted disease requires screening for HIV, hepatitis B, and other STDs.

TABLE 2121 Common Bleeding Manifestations in Patients with Hemophilia

Unfortunately, bleeding is not the only problem facing patients with hemophilia. Many hemophiliacs also have chronic hepatitis and are infected with the human immunodeficiency virus type 1 (HIV-1) as a result of their exposure to blood products. In hemophilic patients who received plasma products prior to the mid-1980s, 90 percent have serologic evidence of hepatitis B, 85 to 100 percent have hepatitis C antibodies, and 60 to 90 percent have HIV-1 infection. Those most likely to be infected with HIV-1 are patients with severe hemophilia A without an inhibitor. Hemophilia B patients are less likely to be infected with HIV-1 as a result of the products they receive for treatment about 50 percent are infected. Since 1985, acquired immunodeficiency syndrome (AIDS) has become the leading cause of death in patients with hemophilia. Hemophilic patients with AIDS account for 1 percent of the total U.S. AIDS population. Since 1986, as a result of new viral inactivation procedures, there have...

Management of Factor VIII Deficiency Hemophilia A without an Inhibitor

Patients with moderate or severe hemophilia A and significant bleeding will require treatment with factor VIII concentrates. In settings where virally safe factor VIII concentrates are not available and life-threatening bleeding requires treatment, cryoprecipitate or fresh-frozen plasma (FFP) can be used temporarily however, these products carry a risk of viral transmission, so they should be administered for this purpose only in true emergencies. Each bag of cryoprecipitate contains about 100 units of factor VIII. FFP contains 1 unit of factor VIII per milliliter of FFP. Most patients with hemophilia A without an inhibitor are treated with factor VIII products made by recombinant DNA technology. T.a.ble ,.212.-.3 outlines the currently available factor VIII concentrates. Other products of lesser purity, which carry some small risk of hepatitis transmission (but not HIV-1), may still be available and used electively by some patients who are already infected, because of their lower...

Fish and Shellfish Allergies

Persons who eat shellfish raw should beware. Raw shellfish may contain the organisms that cause hepatitis and other diseases. Cooking will kill any microorganisms in shellfish. In addition, because shellfish filter large amounts of water each day, they may contain residual amounts of any pollutants in the water near them. Concerns about potentially harmful chemicals are also a concern about shellfish. Women who are pregnant or thinking about having a child should check with their physician about how much shellfish they should eat.

Multiplex Nasba And

The Procleix human immunodeficiency virus-1 hepa-titis C virus (HIV-1 HCV) assay (Gen-Probe Inc.) detects both HIV- and HCV RNA in 1 tube. 8 The source of the reactivity can be determined by discriminatory assays using virus-specific probes. The HIV-1 HCV assay and the discriminatory assays are able to detect 10-13 copies of HIV-1 mL with 95 detection rates, and can detect 30 copies mL of HCV with 95 sensitivity. Furthermore,

Foodborne Viruses and Human Diseases

Hepatitis A Hepatitis A (shellfish, vegetables, milk) Hepatitis E Hepatitis E (clinically indistinguishable from hepatitis A disease, water-borne, person to person) Acute hepatitis is a common disease and is caused mostly by virus infections. At least five hepatitis viruses (A, B, C, D, and E) are pathogenic to humans. Hepatitis A is infectious hepatitis, transmitted via the anal-oral cycle. The incubation period is between 15 and 20 days. Hepatic infection produces a debilitating low-mortality disease. The liver becomes inflamed, enlarged, and tender, the symptoms usually subsiding after 2 to 4 weeks. Some outbreaks have been associated with food (including meat, poultry, and egg products) contaminated by infected food handlers. In the U.S., there has been an increased incidence related to contaminated shellfish consumption, particularly oysters and other molluscs. Another potential source is vegetables contaminated in the field via irrigation with water polluted with human...

Replication And Infectivity

Mousepox (ectromelia) virus was first recognized as a mouse pathogen in 1930. Its pathogenesis differs from other orthopox viruses in that the virulent strains induce severe hepatitis in mice. It is highly infectious and can easily decimate mouse colonies in laboratories and breeding facilities. Vaccinating mice with the Vaccinia confers protection and has been used to control infections in mouse colonies. 7 No human infections have been reported due to ectromelia. However, the virus was useful as model to study the molecular basis of Orthopoxvirus virulence despite the fact that the mouse disease differs significantly from smallpox.

Designed Host Cells Combined

Lessons learned from HIV screens can be transferred to other fields of infectious diseases. For example, the recent development of replicon systems for HCV has led to in-vitro drug screens 86 against this serious chronic disease that affects 170 million people worldwide. The HCV replicon is a subviral RNA molecule maintained within the host cell without extracellular states. The variations for cell-based screens include systems with specially selected cells that support robust replicon expression, and replicons that carry and express reporter genes to facilitate quantification of interfering drugs in high-throughput systems. Highly illustrative with respect to this chapter, HCV replicons have been created that release HIV Tat to activate a stably inserted LTR-reporter cassette in HCV-permissive Huh-7 cells 87 . The in-vitro screens have already yielded a number of promising compounds directed against viral proteases and polymerases. In addition, the in-vitro study of the complete life...

Parvovirus Infection And Immunity

Parvoviruses infect many animals including humans, and almost every species has its own parvovirus pathogen. Epidemics in dogs, swine, geese and mink are major practical concerns of veterinarians. Because of the requirement for actively proliferating cells, the developing fetus and the newborn are at highest risk of disease following parvovirus infection. Infection can lead to fetal death, congenital malformations or predominant damage to single organs that may not be manifest until weeks after birth, such as the cerebellar ataxia that follows in utero feline parvovirus infection. Parvovirus infection of young animals can be clinically severe, with manifestations of encephalopathy, hepatitis or myocarditis. Parvoviruses cause a variety of diseases in adult animals, including gastroenteritis in cats, dogs and mink, leukopenia in cats, and immune complex glomerulonephritis in mink persistently infected with Aleutian disease virus. The human parvovirus B19 was discovered by Yvonne...