Alternative Hepatitis C Treatments

Alternative Hepatitis C Treatments

The therapeutic goals of Natural treatment for Hepatitis C are as follows: Decrease iral load Normalize liver enzyme levels. Enhance/regulate immune system function. Strengthen and promote healthy liver function. Protect the liver, prevent further damage. Virological response; i.e. viral clearance, viral reduction or elimination of the virus. Starve the virus by limiting levels of iron. Optimizing cellular levels of glutathione in the body, making detoxification of the liver possible and enhancing the immune system. Stimulate regeneration of the damaged liver cells. Use of antioxidants to combat the effects of free-radicals generated by the virus. Reduce inflammation. Slow viral replication. Replace all of the inflammation-damaged liver cells. Regulate immune function/prevent auto-immune problems. Cancer preventative measures. Reverse fibrosis to prevent and improve cirrhosis

Alternative Hepatitis C Treatments Summary


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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.

Hepatitis B Virus Infection And Immunity

Damaged Hgv Tyre Pictures

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...

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...

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 is most commonly caused by a virus. More than 90 percent of cases of viral hepatitis in humans are caused by five viruses HAV, HBV, HCV (or classic non-A, non-B hepatitis virus), HDV (or delta agent), and hepatitis E virus (HEV) or epidemic non-A, non-B hepatitis virus . These five viruses are each very different and share only a common tropism for the liver, with the hepatocyte representing the dominant site for viral replication and acute or chronic hepatitis as the major clinical manifestation of infection. The viruses can be divided into two distinct groups based upon the existence of a lipid-containing outer envelope.38 HBV, HCV, and HDV all possess a lipid-containing outer viral envelope. HAV and HEV, lacking a lipid envelope, are stable when secreted from infected hepatocytes into bile and thus gain entry into the gastrointestinal tract. These viruses are spread by the fecal-oral route and can cause extensive single-source outbreaks of disease. HAV and HEV do not...

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...

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 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...

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.

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...

Renal Anatomy and Basic Concepts and Methods in Renal Pathology

Nephronophthisis Kidney 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...

Immune responses of the host

The sensitivity of the current serological assays is such that specific antibody responses arc detectable in the vast majority of HCV-infected individuals. The only exceptions to this are patients who are immuno-suppressed at the time of infection, where RT-PCR positivity may be the only indication of infection, and in the weeks following acute infection, as it may take up to 6 months for anti-HCV reactivity to develop. The clinical and biological significance of antibodies to HCV-derived polypeptides present in diagnostic assays is still unknown. They are clearly not protective, as the majority of anti-HCV positive sera are also RT-PCR positive. It is possible that antibodies against the envelope glycoproteins may have neutralizing activity, but assays for the detection of anti-El and -E2 are not widely available, and neutralization studies are severely hampered by the lack of a routine cell culture system for HCV.

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.)

[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...

Clinical Features

The sudden appearance of jaundice in a previously healthy young person, especially if preceded by a brief prodrome of fever, malaise, and myalgias, is likely to be caused by a viral hepatitis. Inquire about body fluid exposure over the previous few months, including transfusion of blood products, intimate contact with someone with hepatitis or jaundice, promiscuous sexual activity, intravenous drug use, accidental needle-stick injuries or mucosal contact with body fluids, travel to countries where hepatitis is prevalent, raw shellfish ingestion, and recent tattoos or body piercing. Many times, however, no history of exposure can be elicited. Right upper quadrant pain and tenderness and hepatomegaly may be present, but pruritis is usually absent. Examine for needle tracks, since patients may not volunteer a history of drug use. Jaundice that develops gradually and is accompanied by weakness, peripheral muscle wasting, ascites, spider angiomata, pruritus, and symptoms of portal...

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.

Evasive strategies by the organism

Evasion of the immune system by picornaviruses is primarily by antigenic variation of neutralizing antibody epitopes but may also involve variation at T ccll sites MHC-binding motifs leading to compromised help for humoral immune responses and cell-mediated killing of infected cells. However, persistent infections may be another mechanism by which these viruses can survive in the presence of circulating antibody. Hepatitis A virus appears to be anti-genically very stable and little is known about how this virus may evade the immune response. Antigenic epitopes lie on the surface of the virus and are generally located on the loops which join (3 sheets. These loops are less constrained in both amino acid type and length. Many of these epitopes have been mapped by sequence analysis of monoclonal antibody neutralization-resistant mutant viruses.

Risks from Cell Lines

For most routine cell culture laboratories, the major concerns will relate to the potential for cell contamination with serious human pathogens that would put laboratory workers at risk (e.g., HIV1 and 2, HTLV I and II, hepatitis B). Testing cell banks for such viruses can provide confidence in the safety of work with cell lines, though this is dependent on the availability and quality of the testing performed. A negative test which is not adequately sensitive or not appropriate (e.g., it detects antibody response to viral infection only found in blood samples, not qualified with cell lines) may in fact be dangerous in that it could give false confidence to laboratory staff by giving false-negative results. Such testing should be considered carefully and carried out by an accredited laboratory.

Quantitative Nasba And Tma Applications

Quantitative nucleic acid amplification tests are gradually introduced into the laboratory. These assays are used for determination of the viral load of patients infected with blood-borne viruses such as human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). The conserved 5'NCR of HCV has been used as a target for the development of qualitative and quantitative ECL-based NASBA assays for genotypes 1a, 1b, 2, 3, 4, and 5. 16 When different assays were compared, the HCV NASBA-QT assay was over 10 times more sensitive than the bDNA assay, while the quantitative results of both assays were highly concordant. The HCV NASBA- QT assay was comparable in sensitivity with the HCV MONITOR assay (Roche Molecular Systems), but the latter yielded consistently lower values. 16 The qualitative COBAS AMPLICOR HCV version 2.0 PCR assay (Roche Molecular Systems) and the VERSANT HCV RNA qualitative assay (Bayer) were compared for analytical sensitivity and clinical perfor-mance. 17 The...

Application for Other Organisms

Pseudomonas aerugenosa. 24 Furthermore, ribotyping has been applied successfully in many studies to differentiate bacterial strains. 25,26 Other applications of locus-specific RFLP found place in epidemiological studies of hepatitis C virus (HCV). By this technique, the virus can be subtyped into six major genetical groups. 27 The RFLP of the 5' untranslated region has facilitated studies of the geographical distribution of viral genotypes and natural history of the disease.

The etiological role of viruses

Retroviruses are known to infect cells of the immune system and can cause abnormalities of immune regulation including suppression, destruction or stimulation of T cells, excess antibody production and lymphomas. A subgroup of patients with human immunodeficiency virus (HIV) infection develop diffuse infiltrative lymphocytosis (DIES) of salivary glands and other organs with predominantly CD8+ T cells. They may present with a clinical picture almost indistinguishable from primary SS. In addition there is a high frequency of extraglandular disease including lymphocytic interstitial pneumonitis, lymphocytic hepatitis, lymphocytic interstitial nephritis and lymphocytic aseptic meningitis. In spontaneously occurring SS retroviral A-type particles were identified in lymphoblastoid cells cocul-tured with homogenates of salivary glands from SS patients but there has not been any further information such as sequence data to characterize the virus. A number of studies have detected antibodies...

Protozoal encephalitis see Chapter

Toxoplasmosis is often suspected in cats with neurological signs. However, Toxoplasma gondii is an opportunistic pathogen and while subclinical infection is common, clinical disease occurs rarely. Cats are the definitive host. There is no breed, sex or age distribution, but immunosuppression, concurrent illness or drugs can predispose to development. The most frequent systemic manifestations are hepatitis, pneumonia, iridocyclitis and chorioretinitis. Neurological signs, if they occur, are referable to a multifocal nonsuppurative encephalomyelitis, but occasional focal lesions are present. In young cats, a generalised myositis and inflammation of nerve roots is a more common manifestation. Most cases of toxoplasmosis are acute, with a clinical course of a few weeks.

Stress and immunity in human studies

Four examples serve to illustrate this. In a 1-year study of a group of medical students, there was a strong association between examination stress, increased incidence of illness, and depression of various immunological measures. At times of examination stress, those students who were chronic carriers of latent Epstein-Barr virus (EBV) exhibited increased antibody titers against EBV, which is indicative of virus reactivation. In a further group of students who were immunized with hepatitis B virus vaccine at examination time, those who serocon-verted early were significantly less stressed and anxi

Universal Precautions

The risk of infection via an occupational exposure has been well studied and varies according to the pathogen and type of exposure. Percutaneous exposures are the greatest risk of bloodborne pathogen transmission to health-care workers.21 Of the three most concerning causes, hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV), only HBV has a vaccination that can prevent transmission of this virus. For unvaccinated personnel, the risk of transmission via percutaneous exposure from a HBV antigen-seropositive source is at least 30 percent.22 For HCV and HIV, the risk of infection is far less following a percutaneous exposure, however this is more than offset by the lack of vaccination prophylaxis available at present. Recent literature places the risk of transmission after a single percutaneous exposure from a seropositive person at 0-7 percent for HCV23-25 and at approximately 0.3 percent for HIV.26-28 Variables that may alter the risk following...

Herpes Zoster Shingles

Immunocompromised patients have an increased risk of disseminated disease. This can be recognized clinically by evidence of the rash involving more than a single dermatome or crossing the midline. Disseminated disease may occur in patients with skin lesions limited to a single dermatome. Patients with disseminated disease may develop pneumonitis, hepatitis, meningoencephalitis, or other organ system involvement and should be admitted for IV acyclovir. Immunocompromised patients with shingles without evidence of dissemination can be treated as outpatients with oral acyclovir at the standard dosing, with instructions to return if the rash spreads or if they develop respiratory symptoms, headaches, or other signs of organ system disease. Close follow-up with their primary care provider is recommended.

Biomedical Diagnosis and Classification

Other key signs that physicians look for include color of stool. Green is said to indicate bacterial infection bright red is a sign of bleeding from the lower bowel or hemorrhoids. Black (sometimes referred to as coffee-grounds effect) is indicative of bleeding from the stomach and upper portions of the digestive tract. The blood is black because it is partially digested. The appearance of the profuse liquid stools characteristic of cholera are known as rice water stools. White or very light stool may be associated with hepatitis or other liver problems that impede the ability of the liver to remove the bilirubin

Cultural Overview

Been quite slow compared with other indigenous societies of South America. In Venezuela, Yanomami territory is protected to some extent as a United Nations Biosphere Reservation. However, on the Brazilian side of the territory, road construction and an invasion of miners between the 1970s to 1990s has brought considerable illness and death. International protests forced the Brazilian government to take decisive steps to put an end to this disastrous situation. Now the Yanomami are trying to deal with the consequences of the intrusion with the help of social workers and anthropologists. A demographic increase observed in the late 1990s should not hide the fact that illnesses like malaria, influenza, tuberculosis, and hepatitis are severe threats to all the Yanomami. Epidemics have the potential to wipe out entire communities within a short time if no professional help is available. The miners and the Brazilian government have also failed to keep their promises to grant land rights to...

Screening for infectious agents

Since the 1970s donors have been screened for hepatitis B virus infection and for syphilis. Alanine aminotransferase is used as a surrogate test for early viral hepatitis A, B and C or non A, non B, non C hepatitis. Major improvements were brought forth by the introduction of testing for human immuno deficiency virus (HIV) in 1985 and for hepatitis C virus in 1990, rendering the blood supply today safer than ever. The rate of infectious units in the blood supply varies considerably among different populations and over time within a population. It depends on the endemic diseases, the selection of the donor populations and their epidemiologies, which need to be monitored on a continuous basis. Because infectious donors may be missed during the diagnostic window, both the incidence of infections and their prevalence are important parameters. Removal of white blood cells, which serve as a shuttle for some-viruses, may limit viral transmission. Plasma is often quarantined for 6 months...

Liver transplantation

Fulminating hepatitis while successful correction of mctabolic defects, e.g. a,-antitrypsin deficiency, may also be achieved by liver transplantation. Technically liver transplantation is the most difficult of the organ transplants, the liver being placed in the bed of the patient's own liver which is first removed (orthotopic transplant). However, most of the technical problems have been resolved and 1-year graft survival both in adults and children is around 65 , with full rehabilitation of patients with a successful transplant being achieved.

Sampling Errors Differential Enrichment and Recovery During Culture

Treponema pallidum PCR for hepatitis C virus In viral load assays conducted to predict the prognosis of patients with HIV and hepatitis C virus, the expense of commercial test kits precludes monitoring with the frequency that might be useful. The sample is a biased one, taken perhaps every 3 months and may not be helpful for showing variations in viral load in the period between samples. As quantitation is the vital aspect of viral load monitoring, factors that alter the number of virions such as delays in transport and processing may lead to errors in assessing this prognostic indicator. Similar considerations apply when sampling shellfish beds for viruses. Representative samples must be taken from the bed to allow for spatial variations, quantity of virus will be affected by the species of shellfish and its filtration rate, and transport and processing should be prompt and temperature controlled.

DNA Vaccination Techniques

As of December 2001 there are several clinical studies in progress to evaluate the effectiveness of DNA vaccination. Most of these studies were targeted against viral infectious agents, such as HIV, hepatitis B, and influenza virus. However, there are also studies in progress to develop DNA vaccines against malaria and tuberculosis. There are even several efforts to develop DNA vaccines against various forms of cancer, an approach which seems to offer significant hope for the future. see also Immune System Genetics Plasmid.

Other childhood vaccines

More recently, the IOM has published findings on adverse events associated with a number of other childhood vaccines, to see whether any evidence bearing on causality could be established. Reactions to the diphtheria and tetanus toxoids, measles, mumps, polio, hepatitis B, and Haemophilus influenzae type B (Hib) vaccines, were examined. Evidence for neurological disorders (both demyelinating and nondemyelinating diseases) and a series of immunologic reactions (anaphylaxis, Arthus reaction, delayed-type hypersensitivity and autoimmunity in particular) was sought. After an exhaustive review of the available data, the findings suggested that these vaccines are remarkably safe.

Reading and Interpretation Errors

Misinterpretation of typing may occur and it is important to focus on clinical problem-solving rather than modern methods alone. Typing is not mystical. Its goal is simply to provide evidence that epidemiologically related isolates are also related genetically, represent the same strain, and thus may have a common origin. In larger-scale studies, it may also suggest that genetically related isolates have a common epidemiological source. This may be harder to prove with certainty and gives potential for falsely positive associations that could have costly implications for the agricultural and food industries if food products are mistakenly implicated by overzealous investigators. An outbreak can occur with more than one epidemic strain, and an outbreak is not excluded because of strain heterogeneity (205). Hepatitis C viral quasispecies, heterogenous mixtures of virus particles containing hypervariable regions, sequentially change during the natural course of infection and the...

Persistent viral infections

Many viruses are able to maintain long-term infections which are often symptomless. This may involve chronic production of infectious virus, or latent infection with intermittent reactivation leading to virion production. Certain viruses may exhibit both patterns dependent on host cell type - for example, hepatitis B virus appears to latently infect lymphocytes but produces infectious virus in hepatocytes. In order to establish a successful persistent infection, a virus should minimize damage of host cells. Certain noncytopathic viruses such as the murine arenavirus LCMV replicate with little apparent disruption of cell function. Other viruses have evolved different strategies that can reduce their lytic potential. These include restricted virus gene expression (in the herpesviruses during their latent nonlytic infection of neuronal or lymphoid cells) the generation of mutant viral strains which do not cause cell lysis (in reovirus after in vitro passage in fibroblast lines) and...

The Alcoholabusing Patient

Although alcoholism by itself is not a medical emergency, alcohol abuse and dependence are common threads in the presentation of many conditions in the emergency department. Such presentations include trauma, infections, acute alcohol intoxication and withdrawal, hepatitis, and pancreatitis. Alcohol is often used with other drugs, including cocaine, benzodiazepines, and marijuana. Emergency physicians should recognize alcoholism as both a contributor to a patient's presenting problems and as an underlying problem requiring care itself.

Diagnosing Wilson Disease A High Index Of Suspicion

Liver biopsy with determination of hepatic copper content is the most valuable single diagnostic procedure. Liver copper 250 pg g dry weight is highly suggestive for Wilson disease, but may be also found in cholestatic diseases and in idiopathic copper toxicosis. The major shortcoming of a single liver biopsy specimen is underestimation of hepatic copper because of inhomogeneous copper deposition in the liver. Detection of copper in histological specimens by special staining methods such as rhodamine or orcein staining depends on its intracel-lular localization and is therefore insensitive and rarely helpful in establishing diagnosis. The histological findings in Wilson disease may resemble the features of various other liver disorders such as autoimmune hepatitis or nonalcoholic steatohepatitis.

Membranoproliferative Glomerulonephritis

Membrane Basale

Intracapillary deposits with vague, short fibrillary substruture, in MPGN caused by hepatitis C-associated cryoglobulin (electron microscopy). Figure 3.6. Intracapillary deposits with vague, short fibrillary substruture, in MPGN caused by hepatitis C-associated cryoglobulin (electron microscopy). The MPGN lesions have been recognized to occur secondary to a number of chronic infectious processes, including hepatitis B, hepatitis C, syphilis, subacute bacterial endocarditis, etc. Membranoproliferative glomerulone-phritis may rarely occur due to inherited deficiency of complement, or partial lipodystrophy. If a chronic bacterial infection is causing MPGN-type lesions, hump-type subepithelial deposits may be present (see Chapter 5). Generally, morphologic features do not allow precise classification of the underlying agent in most cases of type I MPGN. However, a large number ( 25 in the United Sates) of previously idiopathic MPGN cases in adults have been associated with...

The Course of Infectious Diseases

Printable Jewelry Design Grids

The incubation period lasts from the time of ingress of the infection into the macroorganism till the time when the first clinical symptoms become manifest. Each disease has its specific incubation period during which the clinical symptoms are absent. The pathogenic agent multiplies and disseminates in the body during the incubation period, the length of which varies from few hours (food poisoning) to several days (plague, cholera, typhoid fever), weeks (viral hepatitis A), months (viral hepatitis B, rabies), and even years (leprosy). Infectious diseases can be followed by specific complications. Otitis, lymphadenitis or nephritis can complicate scarlet fever, while typhoid fever can be complicated by intestinal haemorrhage or perforation of the intestine some complications can be non-specific, i.e., caused by some other microorganisms. The most dangerous complications of infectious diseases are shock, renal encephalopathy (viral hepatitis), acute renal failure (meningococcal...

Active Demand Passive Acceptance

Hepatitis B vaccine in Delhi as protection against pilia (jaundice), the authors note that medically, jaundice can be caused by different types of hepatitis. Hepatitis A is common in the community and this vaccine does not protect against it. The authors argue that a future problem for the hepatitis B immunization program is that it will in fact not prevent jaundice from occurring. If a child, despite having been vaccinated, falls ill with pilia (caused by hepatitis A) then the mother's faith in the immunization program may be shattered (Addlakha & Grover, 2000).

Is DNA Hypomethylation Like DNA Hypermethylation Sometimes Associated with Tumor Progression

Hypermethylation of a subset of CpG islands is progressive in some types of cancer although sometimes this regional hypermethylation occurs very early in tumorigenesis, and other times it can serve as a significant indicator of survival.16,82, 3 Also, DNA hypomethylation is sometimes associated with tumor progression as seen in studies of repeated DNA sequences. In a study of 31 hepatocellular carcinomas by Itano and coworkers,84 the degree ofhypomethylation of either of two repetitive sequences was significantly correlated with postoperative recurrence of hepatocellular carcinoma and was a better predictor than conventional factors. These repeats were the above-mentioned 1.4-kb Y10752 NBL2 sequence that is found in the pericentromeric regions of chromosomes 13, 14, 21, and 950 and a 13-kb repeat present in tandem about 200 times on 8q21. Hypomethylation was determined by quantitating the corresponding radioactive spots relative to reference spots by restriction landmark genomic...

Gastrointestinal Complications

Hepatomegaly occurs in approximately 50 percent of AIDS patients. Elevation of alkaline phosphatase levels is frequently seen. Jaundice is rare. Coinfection with hepatitis B and hepatitis C is common, especially among injected drug users. Opportunistic infection with CMV, Cryptosporidium, M. avium intracellulare, and MTB may also cause signs of hepatitis.

Medical Clearance For Detoxification

Inquire about past history of hospitalization for delirium tremens, alcohol-related seizures, hepatitis, and pancreatitis screen for severity of alcohol withdrawal signs and symptoms review past medical illness and medications and rule out underlying medical conditions related to substance abuse.

Therapeutic use of IFNa

Effects, including fever, headache, chills, fatigue, anorexia, leukopenia and thrombocytopenia. Despite their current limitations, IFNs are now well established as useful drugs. IFNa is the most widely used and has received approval in many countries, including Food and Drug Administration (FDA) approval in the US, for several clinical indications. Since 1986 it has been used as a therapy against haii v-cell leukemia. Significant regression of the cancer is observed in more than 90 of patients. Since 1988, IFNa has been successfully used as a therapy against diseases associated with human papillomavirus infection such as juvenile laryngeal papillomatosis and condyloma acuminatum. Since that same year it has also been used in the treatment of Kaposi's sarcoma in patients infected with HIV. Around 30 of the patients who reccive IFNa, however, withdraw from treatment because of side-effects associated with the high IFNa doses. In 1991, IFNa was licensed for the treatment of chronic...

Vaccination Programs their Culture and Context

Another anthropological enquiry in India focused on the introduction of a new vaccine, hepatitis B, in the East Delhi Immunization program (Addlakha & Grover, 2000). This program was launched with the WHO in 1996. Addlakha and Grover did ethnographic fieldwork with an aim of (1) understanding the way in which the discourses of public health officials are framed within a meta-discourse of population regulation or biopower, and (2) exploring the lived experiences of actual users negotiating with health problems in specific local settings. They argue that immunization programs regulate populations through a strategic alliance between the immunizing state, multinational pharmaceutical companies, and the medical profession. In the case of hepatitis B vaccination, clinicians from different medical specialities, multinational pharmaceutical companies, and international organizations were trying to persuade the entire population of India that it was in the grip of a potentially fatal health...

HUPO reference sample collection protocol

HUPO reference samples were collected at, and using materials from BD Diagnostics. For each ethnic group (Caucasian, Asian American, African American), blood was acquired by venipuncture from one male donor and one female donor. Donors were tested and determined negative for HIV-1 and HIV-2 antibody, HIV-1 antigen (HIV-1), Hepatitis B surface antigen (HBsAg), Hepatitis B core antigen (anti-HBc), Hepatitis C virus (anti-HCV), HTLV-I II antibody (anti-HTLV-I II), and syphilis. Blood intended for plasma preparation was collected into the following tubes BD Plus Plastic K2EDTA, 10 mL, reorder 367525 BD Glass Sodium Citrate, 0.105 m, 10 mL, reorder 366007 BD Plus Plastic Lithium Heparin, 10 mL, 16 x 100 mm, reorder 367880 BD Glass Serum with silica clot activator, 10 mL, 16 x 100 mm, reorder 367820. The collection procedure was as follows. Under the direction of a qualified and licensed physician, trained phlebotomists collected blood from each donor into evacuated blood collection tubes....

Enterohepatic Bile Acid Transporters In Liver Disease

No mutations in the SLC10A1 gene encoding NTCP leading to clinically manifest defects in hepatic bile acid uptake have been characterized thus far. However, a recent study identified ethnicity-dependent single-nucleotide polymorphisms in the SLC10A1 gene that were associated with a considerable decrease in transport function in vitro.39 Thus, genetic heterogeneity in the SLC10A1 gene may play a role in the etiology of hypercholanemia. Furthermore, certain human diseases, such as advanced stage primary biliary cirrhosis40 and cholestatic alcoholic hepatitis,41 are associated with reduced NTCP expression. However, this change in NTCP expression may be a consequence of cholestatic liver injury rather than a cause of it.

Relationship between plasma anxiolytic concentrations and the therapeutic response

Oxidation and conjugation are the principal mechanisms whereby the benzodiazepines are metabolized. Nitroreduction is an additional pathway that is involved in the metabolism of nitrazepam, flunitrazepam and clonazepam. Aliphatic hydroxylation and N-dealkylation are the main oxidative routes and often lead to active metabolites (e.g. diazepam gives rise to desmethyldiazepam, oxazepam and temazepam as active metabolites). The second main mechanism is hepatic conjugation to glucuronic acid. Drugs such as oxazepam, lorazepam, temazepam and lormetazepam are inactivated in this way. The main oxidative pathways are influenced by physiological factors such as age, by pathological factors such as hepatitis and by drugs such as the oestrogens and cimetidine which affect hepatic oxidative metabolism.

Radiological Imaging Modalities

By virtue of its simplicity and availability, transabdominal US still plays a crucial role in detecting and evaluating liver malignancies. Variations in contrast within abnormal liver tissues and between solid or cystic tumors are ideally suited to detection with US. It provides multiplanar imaging with excellent spatial resolution, while hepatic vascular anatomy and patency can be accurately displayed using color Doppler flow techniques.15 US is, however, highly operator dependent and easily restricted by patient habitus or interference by bowel gas and the concealing rib cage. Although sensitivity as high as 94 has been reported for the detection of small hepatomas, results are generally much more variable with sensitivities ranging from 20-76 in the detection of colorectal liver metastases.16,17 Nevertheless, US is suitable for the screening of liver metastases during the follow-up of colorectal cancer, and the development of HCC in patients with known cirrhosis or chronic...

Muscle antigens Smooth muscle

Sera from patients with chronic active hepatitis contain antibodies to smooth muscle antigens that are detectable by IIF and bind smooth muscle of all organs. The major antigen of the smooth muscle is actin. The antibodies belong mainly to the IgG class, but they can also be found in the IgM class. The test is performed on unfixed cryostat sections of rodent stomach as substrate. Smooth muscle antibodies arc found in 40-70 of patients with active chronic hepatitis, with lower titers found in 50 of patients with primary biliary cirrhosis, and 28 of patients with cryptogenic cirrhosis. These antibodies are also found at low titer in patients with acute viral hepatitis, infectious mononucleosis, asthma, yellow fever and malignant tumors (carcinomas of the ovary, malignant melanoma). They have been found in less than 2 of the normal population.

Chapter References

Centers for Disease Control and Prevention Prevention of hepatitis A through active and passive immunization. MMWR 45(RR-15) 1, 1996. 13. Centers for Disease Control and Prevention Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 47(RR-19) 1, 1998.

Seafood Microorganisms Of Public Health Significance

Seafood, particularly shellfish, may contain a variety of pathogenic microorganisms that impose a threat to the consumers' health. These potential pathogens include both indigenous organisms and contaminating organisms. Pathogens may contaminate the seafood after harvest or during processing. Some indigenous pathogens found are Vibrio, Clostridium botulinum type E,Aeromonas, and poisonous phytoplankton such as dinoflagellates (111,112). Extraneous pathogens include Salmonella, Shigella, Listeria, Campylobacter, Staphylococcus aureus, E. coli, Bacillus cereus, Hepatitis A, and Norwalk virus (64,112).

Localization of HEV epitopes

The patterns of viremia and virus excretion arc not well characterized in humans and only limited data exist from experimental animal models (cynomoigus macaques). In humans, viremia has been detected by RT-PCR within 2 weeks after the onset of illness and persists for 4-16 weeks in some individuals. Virus excretion has been detected by immunoelectron microscopy (IEM) in feces, predominantly in the first week following the onset of acute icteric hepatitis, and may persist for 2 weeks, with one report documenting excretion for up to 52 days. In macaques RT-PCR has been used to detect viremia within 4 days after experimental infection, which persists for up to 2 weeks after the onset of illness. Virus excretion in experimentally infected macaques has Morphologic features of HE in liver tissue specimens include those of cholestatic and standard (noncholestatic) types of acute viral hepatitis. In cholestatic HE, bile stasis is observed in canaliculi and gland-like transformation is seen...

TABLE 992 Pregnancy Related Contraindications of Some Frequently Used Antibiotics

Penicillin and cephalosporins are generally regarded as safe for use in any trimester. Neither group has been associated with teratogenesis in either animals or humans. Erythromycin does not cause known adverse fetal effects, but the estolate formulation is contraindicated in pregnancy, since it may cause maternal cholestatic hepatitis. Sulfonamides (including the sulfamethoxazole component of trimethoprim-sulfamethoxazole) are not known human teratogens. Maternal use close to term, however, may cause complications in the neonate. Sulfonamides compete with bilirubin for albumin binding. The fetus clears free bilirubin via the placenta, but in the neonate free bilirubin accumulates and may cause kernicterus. Trimethoprim, the other component of this combination antibiotic, should be avoided in the first trimester, since it is a folate antagonist and may cause neural tube abnormalities. If trimethoprim-sulfamethoxazole offers a clear advantage over other antibiotics, it is reasonable to...

Laboratory Evaluation

A direct-reacting fraction of at least 30 percent (and usually much higher) is present with conjugated hyperbilirubinemia. Conjugated bilirubin is water soluble and appears in the urine at very low serum concentrations. Urobilinogen will be absent from the urine if significant cholestasis is present. If liver enzyme levels are normal, the jaundice is caused by sepsis or recent systemic infection, in-born errors of bilirubin metabolism (such as Rotor syndrome or Dubin-Johnson syndrome), or pregnancy rather than by primary hepatic disease. If liver enzyme levels are abnormal, which is much more common, the pattern of abnormality suggests the cause. Predominance of aminotransferase elevation is more suggestive of hepatocellular disease, such as viral or toxic hepatitis or cirrhosis, while marked elevations of alkaline phosphatase (two to three times normal) and g-glutamyl transpeptidase suggest intra- or extrahepatic obstruction, such as malignancy or gallstones. Further laboratory...

Surgery Of Hepatobiliary Malignancies

Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy, although it is relatively uncommon in Northern Europe. As elsewhere, it is typically recognized at an advanced stage and is generally associated with chronic liver disease. Extensive aggressive surgery is justified as it remains the treatment of choice. Associated cirrhosis (present in over 80 of cases) and chronic hepatitis constitute a significant obstacle to performing major hepatectomy, and only about 20 of all patients with HCC are considered resectable at initial presentation. Although recurrence will develop in approximately 70 of patients after curative resection, a 5-year survival rate of 35 can be achieved.8,9 Early detection by screening high-risk groups and the use of parenchyma-preserving segmental resections are the main reasons for an increase in the number of patients undergoing curative surgery. Specific problems relate to the initial recognition and diagnosis of tumor within cirrhotic liver...

Recombinant vaccines expressing tumor associated antigens

Subcutaneous vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen 71 . After this treatment grade III IV autoimmune manifestations in six patients (43 ), including dermatitis, enterocolitis, hepatitis, and hypophysitis was observed, which recovered completely after stopping anti-CTLA-4 treatment and starting steroid therapy. Interestingly, objective cancer regression was observed in three patients (21 two complete and one partial response). This study can be considered as an important breakthrough, because it establishes CTLA-4 as an important molecule regulating tolerance to 'self' antigens in humans and suggests a role for CTLA-4 blockade in breaking tolerance to human cancer antigens for cancer immunotherapy. This new and powerful modality is thus able to enhance the efficacy of vaccination, and opens perspectives for all active specific immunotherapies.

Body Weight and Energy Balance

The presence of alcoholic liver disease results in significant changes in body composition and energy balance. Although fatty liver is fully reversible, progression to alcoholic hepatitis can have profound effects on nutritional status. According to large multicenter studies, alcoholic hepatitis patients demonstrate universal evidence for protein calorie malnutrition, according to the physical findings of muscle wasting and edema, low levels of serum albumin and other visceral proteins, and decreased cell-mediated immunity, whereas their 6-month mortality is related in part to the severity of malnutrition. Anorexia is a major cause of weight loss in alcoholic liver disease, and may be caused by increased circulating levels of leptin. Furthermore, active alcoholic hepatitis contributes to increased resting energy expenditure as another cause of weight loss. On the other hand, resting energy expenditure is normal in stable alcoholic cirrhotics who are also typically underweight or...

Occupational Risks And Exposures

OSHA defines occupational exposure as a reasonably anticipated skin, eye, mucous membrane, or parenteral contact with blood or other potentially infectious materials that may result from the performance of the employee's duties. 2 OSHA defines blood as human blood, blood products, or blood components. Other potentially infectious materials are defined as human body fluids, such as saliva, semen, and vaginal secretions cerebrospinal, synovial, pleural, pericardial, peritoneal, and amniotic fluids any body fluids visibly contaminated with blood unfixed human tissue or organs HIV- or HBV hepatitis B virus containing cell or tissue cultures, culture mediums, or other solutions and all body fluids where it is difficult or impossible to differentiate between body fluids. Health care workers should treat all bodily secretions, fluids, and tissues as potentially infectious substances. Many infectious diseases can be transmitted via blood or body fluid contamination, including HIV hepatitis A...

Naturalistic Examination Stress

To improve upon some of these shortcomings, Kiecolt-Glaser and Glaser conducted a comprehensive series of studies in which they examined the immuno-modulatory effects of a commonplace, everyday stressor academic examinations. In their standard protocol, medical students were examined at two time points during their first 2 years of medical school first during a lower stress baseline period in which exams were not being given and then a month later during examinations. Results revealed that exam stress was associated with decreased NK activity, decreased lymphocyte proliferation to mitogens, and decreased production of various cytokines. In addition, exam periods were associated with greater self-reports of illness (primarily upper respiratory infections) suggesting that the observed immune changes may have health consequences. Students' levels of plasma albumin and transferrin fell within normal ranges during the exams, suggesting that immune changes were not due to poor nutrition...

Prevention of Infectious Diseases akd IVkasuics to Control luuu

The infectious patients must be isolated in proper time. Patients with plague, cholera, viral hepatitis, typhoid and paratyphoid fever, diphtheria, and similar contagious diseases should be immediately hospitalized. The patients should be handled in special ambulance cars that should be disinfected after transportation of each patient (See Disinfection). The patient delivered to the hospital must be given appropriate sanitary treatment before placing in the appropriate ward or an isolated room, if the diagnosis is not clear, or infection is mixed by its character. Special measures should be taken in order to prevent spread of infection within the hospital. In order to remove the danger of spreading infection, the patient should be given appropriate therapy. Patients with scarlet fever, escherichiasis, dysentery and the like diseases can remain at home where they must be isolated from the other family. The family must be instructed how to prevent infection and to disinfect the...

Prospects for the future

Table 6 gives an estimate of the vaccines which may become available within the next 10-15 years. One development which will need to accompany the release of many new vaccines is the need to make combinations. A major cost in this area is the delivery of vaccines to the populace. The current combinations, MMR and DTP, have been highly successful. Determining those vaccines which might be added to existing combinations, such as hepatitis B and H. influenzae type B, has become a major activity for vaccine manufacturers. Hepatitis A virus Hepatitis C virus

Effect of maternal immunity on the child

Maternal antibodies have dual effects. They supply both passive protection and they prime the immune system of the child for subsequent exposure to antigen. In mice and rats, neonatal priming with idiotypic and anti-idiotypic antibody protects from subsequent infection with the original microbial antigen. This has been demonstrated for E. coli K13, Trypanosoma rhodesiense, rabies virus, hepatitis B virus, Mycobacterium leprae, influenzavirus and Plasmodium falciparum malaria.

Pharmacogenetics and psychopharmacology

Theranostics is said to adopt a broad dynamic and integrated approach to therapeutics which may be of practical relevance in differentiating diseases which are closely associated diagnostically (for example, Alzheimer's disease and Lewy body dementia) by applying a combination of immunoassays that enhance the differential diagnosis. Several biotechnological companies now specialize in designing immunoassays for application to infectious diseases such as hepatitis by genotyping the hepatitis C virus for example. There are six genotypes of the virus known genotype 1 is more resistant to standard therapy (requiring at least one year of continuous therapy) whereas the other genotypes usually respond to treatment within 6 months. Clearly a knowledge of which viral genotype is present is important in determining the duration of treatment in the individual patient and hopefully it will soon be possible to extend such approaches to the drug treatment of...

Newer approaches to vaccine development

Transfection of bacteria is appropriate for generating relatively simple proteins, such as occur in bacteria and some parasites, but limitations on post-trans-lational processing restrict this approach. Trans-fected yeast, the source of the first genetically engineered vaccine, the hepatitis B viral vaccine composed of the surface antigen (HBsAg), has also considerable promise for some other products. For some preparations, e.g. viral glycoproteins, transfected mammalian cells - either primary cells (e.g. monkey kidney), cell strains (a finite capacity to replicate) or cell lines (immortalized cells) - offer great promise. All have been used successfully for veterinary vaccines, and will find increasing use in the future for medical products.

Cholecystitis And Biliary Colic

A number of risk factors are associated with cholecystitis and calculi, including increased age, female sex, parity, obesity, diabetes, profound weight loss, prolonged fasting, cystic fibrosis, intestinal malabsorption syndromes, various medications (particularly oral contraceptive agents and clofibrate), and a familial tendency. Clinical characteristics associated with an increased risk of the development of pigment stones are Asian descent, chronic biliary tract infection, parasitic infection (e.g., Ascaris lumbricoides), chronic liver disease (particularly related to alcohol), and chronic intravascular hemolysis (sickle cell anemia and hereditary spherocytosis). Hepatitis A, B, C, and E HIV and the herpesviruses are associated with viral cholangitis and hepatitis. 4

Epidemiology Foodborne Disease

Travelers are at an increased risk of foodborne illnesses secondary to exposure to new, previously unseen pathogens, increased exposure through meals at hotels and restaurants, and unpredictable standards for public health cleanliness and water-supply systems. 12 The relative risk of foodborne infection with viruses, bacteria, or parasites varies by country, but ranges from 20 to 50 percent for all travelers.1 Enterotoxigenic E. coli is recognized as the major cause of travelers' diarrhea,5 but other strains of E. coli are associated with travel, including enterohemorrhagic and enteroinvasive E. coli.12 The prevalence of Salmonella typhi necessitates typhoid immunization for travelers to many countries.12 Salmonella serotype Enteritidis outbreaks have occurred on airlines and railways from contaminated meals.12 Other pathogens associated with international travel include Brucella, hepatitis A,12 Vibrio, Shigella, Campylobacter, Giardia lamblia, and Cryptosporidium.5

Aflatoxin and Human Cancer

In the early 1990s, nested case-control studies conducted in Shanghai utilized these biomarkers to establish a significant association between afla-toxin exposure and HCC. They showed that the risk of HCC increased dramatically (60-fold) in individuals who had been exposed to aflatoxin and had chronic hepatitis infection compared to those with neither the chemical nor viral exposures. Additional studies in Qidong and Taiwan have confirmed this striking chemical-viral interaction. The underlying mechanism for this interaction remains poorly understood.

Treatment of nausea and vomiting of pregnancy

Cholecystitis, peptic ulcer disease, or hepatitis can cause nausea and vomiting and should be excluded. Gastroenteritis, appendicitis, pyelonephritis, and pancreatitis also should be excluded. Obstetric explanations for nausea and vomiting may include multiple pregnancies or a hydatidiform mole.

B cell deficiency diseases

The physiological importance of B cell function is revealed by diseases that result from selective B cell deficiencies and consequent lack of antibodies (agammaglobulinemia). Bruton's agammaglobulinemia (XLA) is an X-linked defect in B cell maturation in humans, with arrest at the Pre-B I stage and a resulting deficiency in all immunoglobulin classes. A corresponding B cell maturation defect, the Xid mutation, also occurs in CBA N mice. In male children with XLA, the maturation block results from deficiency of a B cell-specific protein tyrosine kinase, btk. With a profound lack of mature B cells but normal T cells, these children are particularly susceptible to infections by bacteria, mycoplasma, hepatitis virus and enteroviruses. They have recurrent middle ear infection, pneumonia, sinusitis and tonsillitis caused by Pneumococcus, Streptococcous and Hemophilus. Problems with infection begin several months after birth, when the pool of protective maternal antibody decreases. XLA...

Liver in Specific Hepatobiliary Disorders Hepatocellular Diseases

Table 1 summarizes the five published controlled trials of the effect of oral or enteral nutritional supplements on patients with alcoholic hepatitis. In most, nitrogen balance and or protein synthesis improved, although no effect on mortality was shown, perhaps because of the small number of patients studied and or the duration of follow-up. In the largest study, at 1-year follow-up, the experimental group had a significantly better survival 2 24 (8 ) died compared to 10 27 (37 ) of the controls. In general, the effects of parenteral nutrition in alcoholic liver disease are similar to those noted the studies of enteral nutritional supplements. A variety of international associations have made nutritional recommendations for patients with various types of alcoholic liver disease. The primary recommendation is of course abstinence, which may be all that is needed in patients with fatty liver. Patients with alcoholic hepatitis should take 40kcal kg, 1.5-2.0 g protein kg, 4-5g kg of...

TABLE 771 Extraintestinal Manifestations of Inflammatory Bowel Disease

Hepatobiliary disease is common in patients with inflammatory bowel disease and includes pericholangitis, chronic active hepatitis, primary sclerosing cholangitis, and cholangiocarcinoma. Gallstones are detected in up to 33 percent of patients with Crohn's disease. Ihe incidence of acute and chronic pancreatitis is increased in patients with Crohn's disease and ulcerative colitis.

Defined Viral and Cellular Pathways and Designed Host Cells

Whilst HAART has significantly increased the quality of life and extended the life expectancy of patients infected with HIV, it cannot yet provide a cure for AIDS. Hence, pharmaceutical research is still faced with the challenge to refine screens in order to identify complementary drugs that specifically target only defined aspects in the life cycle of HIV. Patients infected with hepatitis B virus (HBV), hepatitis C virus (HCV) or certain herpesviruses may also benefit from complementary chemotherapy other pathogens that may be tackled by such approaches include parasites such Plasmodium, the cause of malaria. The principle behind drug screening against HIV therefore is instructive also for other diseases.

Nausea Vomiting and Hyperemesis Gravidarum

Hyperemesis Gravidarum Diet Plan

The presence of abdominal pain in nausea and vomiting of pregnancy or hyperemesis gravidarum is highly unusual and should suggest another diagnosis. Occasionally, women with ruptured ectopic pregnancies present with nausea and vomiting as well as diarrhea and abdominal pain. After the first trimester, the volume of the gallbladder increases during fasting and postcontraction after a meal. Also, biliary sludge seems to increase in pregnancy in 30 percent, predisposing to stone formation.7 Cholelithiasis and cholecystitis are more common in pregnant women than in women of comparable age and health status who are not pregnant. Differential diagnosis of vomiting or vomiting with abdominal pain should include cholecystitis, cholelithiasis, gastroenteritis, pancreatitis, hepatitis, peptic ulcer, pyelonephritis, ectopic pregnancy, and fatty liver of pregnancy.

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,

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...

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 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

Thymic peptides as immunoregulators or biological response modifiers

Peripheral blood mononuclear cells obtained from patients with chronic hepatitis B virus infection have an increased production of IL-2 and TNFa in response to THFy2, suggesting an antiviral role for this peptide in vivo. An effect on hematopoietic progenitor cell proliferation was recently documented in which THFy2 increased the number of myeloid colonies of bone marrow cells from normal mice. Human erythroid and myeloid hematopoietic progenitor cells are also stimulated to growth by THFy2. Combination therapies with Tal are used in infections and tumors, for example, AZT, Ta 1 and IFNa in HIV patients. Tal is being used in clinical trials of head and neck cancer, advanced non-small-cell lung cancer and metastatic melanoma. Tal is being used in hepatitis B and C trials worldwide. Other thymic preparations such as thymostimulin (TP1) are used in combination therapies, for example in metastatic colon cancer.

The In Vitro Pyrogen Test Whole Blood Pyrogen Test

Lists 13 exogenous microbial pyrogen and two exogenous nonmicrobial pyrogen classes (the two nonmicrobial classes are drugs and devices plastics) Cites events associated with parenterally manufactured biologicals (most referenced by the group members's own experiences), including immunoglobulins, human serum albumin, hepatitis B vaccine, pertussis vaccine, influenza vaccine, tick-borne-encephalitis vaccine, gentamycin (actually contaminated below or near the limit but given at elevated, off-label dose) A range of sample types according to rabbit, LAL, or IPT test and lists only recombinant proteins as being questionably tested via the IPT Notes that vaccines raise both pyrogen- and LAL-related problems, such as when vaccines derived from GNB contain endotoxin as a component, are inherently pyrogenic although LAL nonreactive, or that contain aluminum hydroxide, which interferes with the LAL test, and finally, the fact that many blood products are incompatable with LAL testing Adherant...

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...

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...

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.

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...

General features of CAH

Chlamydia Trachomatis

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,...

Breast Feeding During Illness

Mothers with hepatitis B can breast-feed their infants if the infant receives the hepatitis B vaccine during the first few days after birth. There is no evidence that hepatitis C is transmitted by breast-feeding. Mothers with chronic hepatitis C are often advised that they can nurse their infants, but they should discuss this with their physician. Other types of infections need to be evaluated by the obstetrician and pediatrician, but nearly all are likely to be safe for breast-feeding.

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

Effects of Alcohol on Liver Function

Progression to alcoholic hepatitis involves invasion of the liver by neutrophils with hepatocyte necrosis. Giant mitochondria are visible and dense cytoplasmic lesions (Mallory bodies) are seen. Alcoholic hepatitis can be asymptomatic but usually presents with abdominal pain, fever, and jaundice, or, depending on the severity of disease, patients may have encephalopathy, ascites, and ankle oedema.

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.

Alcohol and Nutrition

The nutritional status of alcoholics is often impaired. Some of the pathophysiological changes seen in alcoholics are direct consequences of malnutrition. However, in the 1960s, Charles Lieber demonstrated that many alcohol-induced pathologies, including alcoholic hepatitis, cirrhosis, and myopathy, are reproducible in animals fed a nutritionally adequate diet. Consequently, the concept that all alcohol-induced pathologies are due to nutritional deficiencies is outdated and incorrect.

TABLE 824 Differential Diagnosis of Hyperbilirubinemias

Emergency Medicine Differentials

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

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

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.

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.

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.

Effects Of Alcohol On Health

Alcoholics have been estimated on average to have a life span 10 to 15 years shorter than that of moderate drinkers or nondrinkers. 4 Increased mortality rates result chiefly from heart and liver disease, cancer, and accidents. Although the occurrence of coronary artery disease is decreased among alcoholics, heavy ethanol use increases the likelihood of hypertension and can cause alcoholic cardiomyopathy. Ethanol is the most common cause of liver failure both in the United States and worldwide. Fatty liver is present in virtually all alcoholics, while 10 to 35 percent develop alcoholic hepatitis. Heavy ethanol use is also associated with increased risk of cancer of the esophagus, stomach, pancreas, liver, and breast.