Herpes Simplex Ebooks Catalog

Stop Herpes Now

You'll discover: What foods are bad for you, encouraging outbreaks. What foods are good for discouraging outbreaks. The connection between genital herpes and stress. What herbs actually suppress the herpes virus. How to heal your body naturally and safely. How to manage stress in your life.

Stop Herpes Now Overview


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Cytomegalovirus encephalitis

Encephalitis associated with cytomegalovirus is rare in individuals with normal immune systems. In patients with iatrogenic immunosuppression (e.g. organ transplant recipients), cytomegalovirus may cause an acute and frequently fatal meningoencephalitis with a generalized inflammation of the brain. In patients with AIDS, cytomegalovirus may cause a more subtle encephalitic illness, pathologically focal or multifocal, with uncertain clinical correlates and natural history. A more aggressive subacute cytomegalovirus encephalitis seen in as many as 10 per cent of AIDS patients typically strikes the subependymal lining, causing a non-focal encephalitis associated with prominent mental status changes and cranial nerve abnormalities. Without intervention, progression to death in a matter of a few months is frequent. This syndrome may be mistaken for AIDS dementia complex, but it is more aggressive and is associated with high levels of cytomegalovirus DNA in the cerebrospinal fluid....

Acyclovir and brain biopsy

Since acyclovir is generally a safe drug, empirical administration in cases of suspected herpes simplex encephalitis is justified on clinical grounds or when polymerase chain reaction diagnostic tests are equivocal or unavailable. The role of brain biopsy in establishing the diagnosis of herpes simplex encephalitis remains controversial. Advocates of routine biopsy for patients with suspected herpes simplex encephalitis point out the lack of pathognomonic clinical features in early herpes simplex encephalitis, which frequently create diagnostic confusion, and that acyclovir therapy is not completely without risk, particularly with regard to acute renal toxicity. However, the increasing availability of polymerase chain reaction assays for viral DNA makes these arguments less persuasive. Acyclovir therapy can be suspended if the subsequent clinical course suggests an alternative diagnosis or polymerase chain reaction analysis of cerebrospinal fluid is negative. Brain biopsy is indicated...

Immunity to HSV Infection

The role of the immune response in controlling HSV infections is multi-faceted and complex. This complexity is a function, in part, of HSV being distributed in both neuronal and extraneuronal sites during the primary and latent stages of infection. In addition, HSV persists within the host even in the presence of concomitant immunity by establishing itself as a latent infection within sensory neurons that innervate the sites of peripheral infection. Despite these challenges, considerable progress has been made in defining the immune components that play a key role in the resolution of an HSV infection and, in the case of adaptive immune responses, in identifying the specific virus-encoded epitopes that are recognized by the B and T lymphocytes. Because a comprehensive discussion of the immune response to HSV infections is beyond the scope to this chapter, the reader is directed to recent reviews on this topic for more detailed information (Koelle and Corey, 2003 Khanna et al., 2004)....

Disorders of the Skin and Margin of the Eyelid 35 255 Herpes Zoster Ophthalmicus Definition

Etiology The disorder is caused by the varicella-zoster virus, which initially manifests itself as chickenpox. If activation or reinfection occurs, the latent neurotropic viruses present in the body can lead to the clinical syndrome of herpes zoster ophthalmicus (Fig. 2.14). Symptoms The incubation period is 7-18 days, after which severe pain occurs in the area supplied by the first branch of the trigeminal nerve (the ophthalmic nerve with its frontal, lacrimal, and nasociliary branches). Prodromal symptoms of erythema, swelling, photosensitivity, and lacrimation may occur before the characteristic clear watery vesicles appear. The vesicles burst and brownish scabs form, which are later shed. Blepharitis (see p.33) is also present in 50-70 of all cases. As herpes zoster usually affects immunocom- Herpes zoster ophthalmicus. Herpes zoster ophthalmicus. Fig. 2.14 The facial rash of herpes zoster is caused by the neurotropic varicella-zoster virus. After the clear watery vesicles burst,...

The Impact of Stress on Primary HSV Infection

Therefore, the impact of a stressor on the immune response during the primary HSV infection may have consequences on not only one's initial encounter with HSV but also on the development of recurrent HSV infections throughout the lifetime of the host. Studies in humans have indicated that stress can affect the frequency, severity, and duration of HSV infection. A number of murine studies during the past 15 years have substantiated these findings by providing compelling experimental evidence that stress and stress-induced, neuroendocrine-derived products increase the development and severity of HSV infection in both the periphery (Bonneau et al., 1991a Kusnecov et al., 1992 Bonneau et al., 1997 Brenner and Moynihan, 1997 Wonnacott and Bonneau, 2002) and the central nervous system (Anglen et al., 2003). For example, mouse models in which either a restraint (Bonneau et al., 1991a Wonnacott and Bonneau, 2002 Ortiz et al., 2003) or footshock (Kusnecov et al.,...

The Impact of Stress on the Memory Immune Response to HSV Infection

Immunological memory is a key component of the overall immune response and is important in reducing the severity of recurrent HSV infection. Because recovery from recurrent HSV infections is largely controlled by T lymphocytes, the ability to generate a population of HSV-specific CTLm during the initial infection with HSV is thought to be critical for the long-term defense against recurrent HSV infection.The psychological stress that is often associated with the primary episode of infection, as well as the development of recurrent disease, emphasizes the potential significance of the effect of stress on the development of HSV-specific T cell-mediated immunity. In studies to date, restraint stress has been shown not to suppress the generation of CTLm in response to systemic HSV infection. However, such a stressor has been shown to be effective at inhibiting the activation of CTLm (Bonneau et al., 1991b, 1996 Leo et al., 1998) and their migration to the site of recurrent HSV infection...

The Role of Stress in Preventing HSV Infections

Given the role that the immune system plays in the resistance to many viral infections, including HSV, vaccination remains an often desired strategy by which to confer protection. However, identifying the salient immune components that are involved in this protection may represent an obstacle to the design of an effective vaccine. The complex nature of HSV infections may also provide a formidable challenge to the development of a vaccine that would be effective at all stages of infection and at multiple sites within the body. Even if a vaccine were to be developed, the fact that stress has been shown to suppress the induction of vaccine-induced immunity (Glaser et al., 1992 Kiecolt-Glaser et al, 1996 Vedhara et al, 1999 Glaser et al, 2000 Burns et al., 2002 Miller et al., 2004) suggests that not all individuals who are vaccinated may necessarily be protected. Moreover, the impact of stress on the reactivation of immunological memory may suppress vaccine-mediated protection against...

Cytomegalovirus Retinitis Human Immunodeficiency Virus Retinopathy

In contrast, acute toxoplasmosis retinitis 14 or cytomegalovirus lesions 5 exhibit enhanced backscat-ter due to inflammation primarily affecting the neurosensory retina. Chronic lesions progress to retinal atrophy and fibrosis, which are evident on OCT as increased retinal reflectivity, marked retinal thinning, and increased penetration of the probe light into the choroid.

Antiherpesvirus Agents

The following drugs are used primarily in the treatment of herpesviruses. Among these are herpes simplex virus-1 (HSV-1), which typically causes herpes labialis (cold sores) or herpes esophagitis herpes simplex virus-2 (HSV-2), which is responsible for most cases of genital herpes varicella zoster virus (VZV), which produces chickenpox and shingles Epstein-Barr virus (EBV), which is the major cause of infectious mononucleosis and cytomegalovirus (CMV), which can produce pneumonia, gastroenteritis, retinitis, encephalitis, and mononucleosis in immunocompromised individuals.

Congenital cytomegalovirus disease

Cytomegalovirus is part of the herpes virus group, and as such it shares a characteristic ability to remain dormant within the body over a long period. It is the most common cause of intrauterine infection, with about 1 per cent of all newborns infected in utero, and is the most common cause of congenital deafness and mental retardation 58 Of those infected, about 10 per cent will have the syndrome at birth. Up to 30 per cent will die and 90 per cent of the survivors will develop long-term sequelae such as microcephaly (70 per cent), mental retardation (60 per cent), neuromuscular disorders (35 per cent), hearing loss (30 per cent), and chorioretinitis or optic atrophy (22 per cent). The presence of chorioretinitis usually indicates significant mental retardation. Of the 90 per cent of those who are asymptomatic of clinical disease at birth, 5 to 17 per cent will develop long-term sequelae. Between 30 and 40 per cent of congenital cytomegalovirus disease occurs due to newly acquired...

Survey of Recombinant Viral Vaccines Currently under Development 6211 Herpes viruses Herpes simplex virus Genital herpes is caused by the herpes simplex virus type 1 or 2 (HSV-1, HSV-2), or human herpes virus 1 and 2 (HHV-1, HHV-2). Subunit HSV vaccines are based upon two envelope glycopro-teins, gB and gD which have been shown to be strongly immunogenic and protective in animal studies (Stanberry 1991). Four separate formulations have been evaluated to date, all derived from CHO expression systems. Three vaccines developed by Chiron contained truncated HSV-2 gD absorbed to alum, gD with a muramyl tripeptide adjuvant, and a bivalent vaccine composed of gD and gB with MF59 adjuvant. Although all these vaccines were immunogenic, the first was only modestly protective, the second caused unacceptable side-effects while the third failed to protect (Corey et al. 1999 Langenberg et al. 1995 Straus et al. 1994 Straus et al. 1997). The fourth vaccine (from GlaxoSmithKline) is also based on truncated HSV-2 gD and alum combined with the novel adjuvant 3-de-O-acylated...

Herpes Simplex of the Eyelids Definition

Etiology Infection of the skin of the eyelids results when latent herpes simplex viruses present in the tissue are activated by ultraviolet radiation. The virus spreads along sensory nerve fibers from the trigeminal ganglion to the surface of the skin. Herpes simplex of the eyelids. - Herpes simplex of the eyelids. -

Kaposis Sarcoma Associated Herpesvirus KSHV or HHV8

In 1994, Chang et al used representational difference analysis (RDA) to search for DNA sequences present in AIDS-associated KS but not in adjacent normal skin. Using this approach, they were able to identify a then unknown human g-herpesvirus in KS tissue, which they called the Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) 5 . KSHV belongs to the genus Rhadinovirus, and its genomic structure is most similar to the closely related lymphotropic g-herpesviruses Epstein-Barr virus (EBV), the only other known human her-pesvirus associated with human cancers. Compelling evidence points to KSHV as the infectious etiologic agent for KS (i) Epidemiological studies have established a pattern of KSHV infection that precedes KS development and overlaps with KS risks. (ii) Examination of KS biopsies revealed that KSHV DNA is present in KS tumor (spindle) cells and in endothelial cells lining vascular spaces of KS lesion. (iii) In vitro studies have demonstrated that...

Herpes Zoster Keratitis Definition

Keratitis due to endogenous recurrence of chickenpox (caused by the varicella-zoster virus see herpes zoster ophthalmicus). Diagnostic considerations Herpes zoster ophthalmicus also occurs in superficial and deep forms, which in part are similar to herpes simplex infection of the cornea (red eye with dendritic keratitis, stromal keratitis, and ker-atouveitis). Corneal sensitivity is usually decreased or absent. Treatment The eye is treated with acyclovir ointment in consultation with a dermatologist, who will usually treat skin changes with systemic acyclovir (in the form of infusions or tablets). If the corneal epithelium is intact, the irritation of the anterior chamber can be carefully treated with steroids and immobilization of the pupil and ciliary body by therapeutic mydriasis.

Antiviral Agent for Treatment of Cytomegalovirus Retinitis

Human cytomegalovirus is a member of the herpesvirus family, which also includes the herpes simplex (discussed below), varicella zoster, and Epstein-Barr viruses (88,89). Cytomegalovirus (CMV) and herpes simplex are the most studied of the microorganisms responsible for the opportunistic infections associated with acquired immunodeficiency syndrome (AIDS) (90). Cytomegalovirus infection in AIDS patients is most commonly manifested as retinitis (CMV retinopathy) and is the most common cause of blindness in AIDS patients (90). Foscarnet (trisodium phosphonoformate) inhibits all human herpes viruses in vitro, including CMV (91), and intravenously administered fos-carnet is currently available for treatment of CMV infections and or retinitis (92,93). The treatment regimen for CMV retinitis consists of an initial induction dose (180 mg kg of body mass per day for 2 weeks) followed by a maintenance dose (120 mg kg day indefinitely) (92,93). Since foscarnet prevents replication of the viral...

Acyclovir and Valacyclovir

Acyclovir (Zovirax) is a guanine nucleoside analogue most effective against HSV-1 and HSV-2, but it has some activity against VCV, CMV, and EBV. Valacyclovir (Valtrex) is the l-valine ester prodrug of acyclovir. Acyclovir is converted to its active metabolite via three phosphorylation steps. First, viral thymidine kinase converts acyclovir to acyclovir monophosphate. Next, host cell enzymes convert the monophosphate to the diphos-phate and then to the active compound, acyclovir triphosphate. Because viral thymidine kinase has a much greater affinity for acyclovir triphosphate than does mammalian thymidine kinase, acyclovir triphosphate accumulates only in virus-infected cells. The active metabolite of acyclovir inhibits her-pesvirus DNA replication in two ways. Acyclovir triphos-phate acts as a competitive inhibitor for the incorporation of deoxyguanosine triphosphate (dGTP) into the viral DNA. In addition, acyclovir that is incorporated into viral DNA acts as a chain terminator...

Herpes Simplex Virus Infection

Herpes viruses are among the most well-studied microorganisms that cause chronic infection and are a well-described cause of ocular diseases (89,102). Ocular degeneration due to infection with herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2) is a leading cause of blinding keratitis in industrialized countries (102,103). Analysis of ocular viral isolates demonstrated that HSV-1 is responsible for about 85 of ocular HSV infections (102,103). Ocular HSV-1 infection consists of an acute keratoconjunctivitis followed by a lifelong cycle of latency, reactivation, and recurrent infection (102,103). This section reviews research on herpetic eye infection and the use of iontophoresis to deliver therapeutic doses of antiviral agents and or agents that cause experimental reactivation of latent HSV-1. b. Antivirals for Treatment of Stromal Disease Hill et al. (107) extended these studies by comparing the efficacy of transcorneal iontophoresis versus intravenous injection of either...

The Impact of Stress on HSV Reactivation and Recurrent HSV Infection

In all but a few cases, a primary infection with HSV resolves within a few weeks and without any long-term consequences. However, the ability of HSV to establish itself in a latent state and to reactivate periodically during the lifetime of the host and cause recurrent lesions is a significant challenge to the development of therapeutic strategies against HSV. There has long been evidence that acute and chronic psychosocial stress can trigger recurrences of both oral and genital infections. Support for this hypothesis has been provided by studies that have demonstrated that emotional stress is associated with the development of recurrent HSV infections (Katcher et al., 1973 Young et al., 1976 Friedmann et al., 1977 Bierman, 1983 Schmidt et al., 1985 Glaser et al., 1987) and that personality may play a role in the frequency of these recurrences (Stout and Bloom, 1986). The severity of HSV infection has also been correlated with psychosocial factors (Silver et al., 1986 Longo and Clum,...

Herpes simplex encephalitis

The herpes family (herpes simplex I and II, cytomegalovirus, varicella zoster, Epstein-Barr) deserves special emphasis because of both the high rates of morbidity and mortality associated with these infections and the availability of effective pharmacotherapy for some. All herpes group viruses contain double-stranded DNA, and Herpes simplex encephalitis is the most common form of lethal non-epidemic encephalitis in the West, with an annual incidence between 1 and 2 per 500 000 persons. Without therapy, mortality exceeds 70 per cent and only about 10 per cent of survivors will regain normal neurological function. In children aged less than 6 months, adolescents, and adults, herpes simplex encephalitis is a focal brain infection, typically localized to one or both temporal lobes or somewhat less frequently the orbitofrontal and mesiofrontal (limbic) regions. In contrast with the neonatal form, which is commonly caused by herpes simplex type II, 'adult' herpes simplex encephalitis is...

Herpes viruses

Epstein-Barr virus is an endemic lymphotrophic herpes virus. Primary infection of the oropharyngeal epithelium produces pharyngitis and subsequent B lymphocyte infiltration. Infection results in lifelong latent infection within lymphoid tissue and B-lymphocytes. A number of EBV encoded proteins have oncogenic potential (EBNA 1 and LMP 1). T-cell surveillance restricts the ability of these proteins to deregulate cell growth apoptosis with consequent emergence of a lymphoproliferative disorder. EBV is associated with a number of human tumours including

Herpes Simplex Virus

HSV is an icosahedral double-stranded DNA virus belonging to the Herpesviridae family of viruses. Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) represent the two antigenically distinct serotypes of HSV. Although HSV-1 is generally considered to be associated with orofacial infections and HSV-2 with genital infections, both serotypes can affect any region of the body. Both HSV-1 and HSV-2 cause a wide variety of clinical syndromes in humans (e.g., herpes labialis, gingivostomatitis, keratocon-junctivitis, herpes genitalis) with the basic lesion being an intraepithelial vesicle from which progeny virus is shed. It is during the primary infection that virus particles first enter sensory nerve endings that innervate the lesion and are then transported to the local sensory ganglia (e.g., trigemi-nal ganglia for orofacial infections dorsal root ganglia for genital infections). Once the virus reaches these sensory ganglia, the virus may either produce an acute infection resulting in...


Epstein-Barr virus (EBV) is a member of the human herpesvirus subfamily Gammaherpesviridae. EBV is an enveloped virus with a double-stranded DNA genome of 172 kilobases (kb) containing more than 100 genes. EBV is a ubiq-uitons virus that infects and persists in about 90 of the world's human population. EBV selectively infects mature B lymphocytes, the only cells bearing the CD21 receptor for virus attachment, recognized by the viral envelope glycoprotein gp350.5 However, natural killer (NK) cells can also be infected with EBV and are associated with unusual malignancies of these cell types. Primary infection with EBV usually occurs in childhood. In most cases, the clinical course is unapparent. In a subset of infected individuals, primary EBV infection can result in infectious mononucleosis, a self-limited lymphoproliferative disease. The syndrome of mononucleosis is more frequent when primary infection is delayed into adolescence. Once infected, individuals become lifelong virus...

Acyclovir aciclovir

It is active against herpes simplex viruses 1 and 2 and varicella-zoster virus, but poorly active against cytomegalovirus. The intravenous route is most reliable and it is distributed to all tissues including the meninges. Acyclovir is excreted by the kidneys and dose reduction is necessary in renal failure, although it is removed by hemodialysis. For the immune-suppressed patient with herpes zoster or varicella, acyclovir prevents dissemination and reduces shedding. It is effective in the treatment of herpes simplex encephalitis. Chickenpox in adults should be treated with acyclovir to reduce the morbidity associated with pneumonia. Phlebitis, reversible renal impairment, and elevation of transaminases are minor side-effects.


The herpes simplex virus causes sores in and outside of the mouth, in the genital areas, as well as other parts of the body. A sign of eruption is a tingling sensation followed by blisters that eventually crust over and disappear. The virus lives in nerve cells, protected from immune-system defenses, and remains dormant most of the time for life. The virus is contracted by skin to skin contact. Triggers that can cause an outbreak are fatigue, viral infections, sunlight, menstruation, and stress. In some people, foods high in the amino acid arginine can bring about an eruption the highest amounts are found in chocolate, nuts, and gelatin. To test for sensitivity to arginine, eat a handful of nuts or chocolate and see if there is a reaction overnight. Shingles or herpes zoster, which is the same virus that causes chicken pox, is characterized by a painful rash usually on one side of the body. Nerve pain, called postherpetic neuralgia, may persist after the rash has disappeared and can...


The use of oral acyclovir (Zovirax ) has proven effective in the treatment of both ocular and nonocular manifestation of herpes simplex virus and varicella zoster virus. The usual regimen for herpes simplex virus is 400 mg 5 times daily. Unlike most oral anti-infectives, acyclovir is able to reach therapeutic levels in the tears and aqueous. Though shown effective when used alone, it is usually paired with topical trifluridine for better action. For varicella zoster infections, the dosage is increased to 800 mg 5 times daily. Even at these concentrations, acyclovir is remarkably nontoxic systemically, normally causing only mild stomach upset on occasion. Zovirax is available as 200, 400, and 800 mg tablets. It can also be found as a 5 dermatologic ointment for treatment of skin lesions. Though shown effective in studies, no topical ophthalmic ointment is available in the United States.

And Herpes Zoster

Chickenpox is a highly contagious infection caused by the herpes virus Varicella zoster. It is typically seen in children where it causes crops of pruritic cutaneous vesicles. It is usually transmitted by direct contact and has an incubation period of 2-3 weeks. The exanthem is frequently preceded by a slight fever, malaise and mild headache. The cutaneous lesions start as an itchy macular rash, which progressively becomes vesicular and pustular before breaking down to form focal crusting lesions. They tend to erupt in crops, but lesions at all stages of evolution are frequently present. The back and chest are often the first sites of involvement, but later lesions appear on the face, neck and limbs. They can involve the nose, ears, conjunctiva and genital areas. In the mouth they form small, non-specific, scattered ulcers. The symptoms last from a few days to 2 weeks. In many cases the virus remains latent in dorsal root ganglia. Herpes zoster (shingles) is due to reactivation of the...

Herpes encephalitis

The chronic memory disorder in herpes encephalitis is often very severe, (25 but it shows many resemblances to that seen in the Korsakoff syndrome, consistent with the fact that there are many neural connections between the thalami, mammillary bodies, and the hippocampi.(28) Encephalitis, like head injury, can also implicate basal forebrain structures which give cholinergic outputs to the hippocampi since these are thought to modulate hippocampal function, this may further exacerbate the damage. Contrary to what was postulated in the 1980s, there appears to be no difference between patients with the Korsakoff syndrome and those with herpes encephalitis in terms of rates of forgetting or in the relative effect upon recall versus recognition memory. The patients with herpes appear to have better 'insight' into the nature of their disorder and a 'flatter' temporal gradient to their retrograde memory loss (i.e. less sparing of early memories), and they may have a particularly severe...

Specimen Processing

The most conventional methods for extracting nucleic acids from clinical specimens involve proteinase K digestion(s) followed by multiple phenol and chloroform isoamyl alcohol (24 1) extractions. The resulting nucleic acids are precipitated in the presence of salts and cold ethanol. The DNA pellet is washed with cold 70 ethanol to remove any contaminants, dried, and dissolved in a suitable buffer system for the ensuing procedures. Although these procedures have proven useful for extracting genomic DNA from tissues, they are often too lengthy and laborious for routine use in a molecular virology laboratory that only tests spinal fluids. In addition, multiple chloroform extraction of specimens containing low copy numbers of viral DNAs can produce false negative reactions because of sample loss. The use of copious amounts of phenol in the laboratory is often undesirable because of the caustic and poisonous nature of these chemicals. The nonorganic salting-out procedures of Miller and...

History Of Viral Vaccines

The first vaccine (Table 1.1), Jenner's smallpox (1798), was produced on the skin of living animals and was a very 'dirty' preparation. The next vaccine, rabies (1885) produced in spinal cord preparations, was equally contaminated with host proteins and caused severe anaphylactic shock and other side effects. The need for cleaner and safer vaccines led to the use of embryonated chicken eggs (yellow fever, 1935 influenza, 1936) and although an improvement, these preparations were still often contaminated with microorganisms. Thus the use of cultured primary cells was seen as a great breakthrough in terms of microbiological quality and purity (i.e. low levels of extraneous contaminating protein). However, subsequent research showed that monkey kidney cells were host to a wide range of intrinsic viruses such as a collection of simian viruses (SV), herpes B virus, etc. Some of these, like SV40, were known to be transforming viruses and thus concerns were felt over the possibility of...

Creation And Maintenance Of Cell Lines Stably And Heterologously Expressing nAChR Of Defined Subunit Composition

Initial success in stably and heterologously expressing a7-nAChR18 can be attributed to selection of host cell (see next section) and selection of vector. The pCEP4 (Invitrogen) vector was chosen because it has the cytomegalovirus (CMV) promoter, which gives high constitutive expression of the downstream transgene of interest in human host cell lines. pCEP4 also contains genes coding for the Epstein-Barr virus nuclear antigen (EBNA) and origin of replication (ORI) allowing episomal replication of the vector in human cells. That is, a vector was chosen that would eliminate a requirement for insertion of the transgene into the host genome, where it might become silenced or subject to variable regulation of expression. This helped to ensure high copy number for the transgene and its stable expression under constant selective pressure via coordinate expression of the hygromycin resistance gene, all from the same plasmid.

Evaluation And Selection Of Donors

Obtaining consent for organ donation is of paramount importance in increasing organ donation. A caring sensitive approach by trained individuals that have time to spend with families cannot be overstated. Organ procurement personnel, clergy, and nursing staff play a vital role in this area. Once consent is obtained, a review of the patient's history should focus on the mechanism of death, periods of hypotension or cardiac arrest, need for vasoactive medications, and previous surgery. Likewise, the patient's social history, including alcohol and drug use, should be known. Generalized infectious diseases are ruled out by obtaining human immunodeficiency virus (HIV) antigen, anti-HIV-1, anti-HIV-2, human T-cell lymphotoxic virus (HTLV)-1 and HTLV-2, anti-cytomegalovirus (CMV), antihepatitis C virus (HCV), hepatitis B surface antigen (HBSAg) and hepatitis B core antibody. Specific organ function is primarily determined by laboratory data, chest x-ray, electrocardiogram, and echocardiogram.

Dynamics of the Vertebrate Nuclear Envelope

The cell nucleus is a complicated organelle that houses the genome of humans and other eukaryotic organisms. Chromosomes are enclosed by the nuclear envelope, and 'communicate' with the cytoplasm by the regulated movement of molecules across nuclear pore complexes. In multicellular animal eukaryotes ('metazoans'), a special set of nuclear membrane proteins and lamin filaments interact with chromatin to provide key structural and functional elements to the nucleus. Remarkably, these structures are reversibly disassembled during mitosis. This Chapter describes the structure and major constituent proteins of the metazoan nuclear envelope, our current understanding of nuclear envelope dynamics during mitosis, and pathways for the reversible breakdown and reassembly of the nuclear envelope and nuclear infrastructure. This field is moving quite fast. A better understanding of these fundamental aspects of nuclear envelope structure and dynamics will provide new insights into an emerging...

Experimental stress and immunity

Naturally occurring human life stresses, both acute (e.g. examinations) and chronic (e.g. caring for patients with Alzheimer's disease), adversely affect a wide array of immune measures ,31 These include T-cell function, NK cell activity, antibody response to immunization, macrophage function, and activation of latent viruses like herpes simplex (controlled by cellular not humoral immunity). Such effects are increasingly being shown to have health implications. Social support can ameliorate stress effects. Natural disasters can have prolonged effects on immunity. (32)

Replication Strategies

Double-stranded DNA viruses (Class I) Viruses of this class have double-stranded DNA genomes and are subdivided into two groups. The first contains viruses that require replication to take place in the nucleus the second class contains viruses that replicate in the cytoplasm. Variola major, the cause of smallpox, is an example of an enveloped double-stranded DNA virus that replicates in the cytoplasm its linear DNA genome is directly transcribed to mRNA, which is then translated by host machinery to produce viral proteins. In contrast, genome replication of herpesviruses occurs in the nucleus.

Expert Committee On The Definition Of Viral Cardiomyopathy

Because isolation of the virus from swabs or tissue is possible in only the acute phase of infection, it is unlikely to succeed in patients with longer-lasting diseases or chronic infections. Enteroviruses, therefore, have been isolated effectively in pediatric patients only. A higher sensitivity is achieved with molecular techniques (eg, gene amplification), which are significantly more sensitive than standard histochemical techniques for the detection of viral proteins. Except for human immunodeficiency virus, hepatitis C, and cytomegalovirus, serologic assessment of antiviral antibodies appeared to be of limited diagnostic value with respect to the actual disease status of the patients and for the critical issue of whether the viral genome is present in the myocardium. The highest sensitivity and reproducibility for the detection of enteroviral genomes were achieved with frozen tissue (100 ) in 5 of 9 centers. Reverse transcription (RT) PCR of enterovirus RNA from fixed embedded...

Drug Transport Across Ocular Barriers

From the drug delivery point of view, monocarboxylate transport processes such as proton or Na + -coupled lactate systems in epithelial cells may serve as conduits for anionic drugs such as cromolyn, which is used in the treatment of vernal conjunctivitis and flurbiprofen and dicolfenac, which are used in the treatment of herpes conjunctivitis. Evidence exists for a Na + -dependent carrier-mediated monocarboxylate transport process on the mucosal side of the conjunctival epithelium (Horibe et al., 1998). This process may be used by ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) and fluoroquinolone antibacterial drugs. While NSAIDs and fluoroquinolones reduced L-lactate transport across conjunctiva, cromolyn and prostaglandins (PGE2 and PGF2) did not affect L-lactate transport, probably because cromolyn is a dicarboxylic acid and the hydrophobicity of PGE2 and PGF2 may hamper their recognition by the monocarboxylate transporter (Nord et al., 1983).

Nucleoside and deoxyribonucleoside kinases

Another member of this enzyme family that has been in focus for pharmacological investigations for two decades is herpes virus 1 thymidine kinase. The enzyme is a dimer of two 44-kDa subunits its specificity towards nucleosides is very broad and many acyclic analogs such as acyclovir and ganciclovir are efficiently phosphorylated.7820 This is the underlying mechanism for the antiviral selectivity of most antiherpes drugs. The literature on the structure and activity of this enzyme in complex with many analogs20 is extensive. The herpes virus type 1 enzyme belongs to a different enzyme family than the adenosine kinases do, but shows high structural similarity with the insect and mammalian deoxycytidine deoxyguanosine kinases as described earlier.19 Herpes TK enzymes have recently received much attention in gene therapy applications.21 This is again due to its broad substrate specificity, which includes L nucleosides and many other antiviral analogs not phos-phorylated by the cellular...

Regulation of Gene Expression

Expression levels of an introduced gene depend mostly on the transduction efficiency of the vector and on the strength of the transcriptional regulatory elements. Typically, strong and ubiquitously active viral promoters such as human cytomegalovirus (CMV) have been used to drive transgene expression (33). A complication of protracted, unrestricted gene expression, which could be offered by many of the newer viral vectors, is the potential for deleterious side effects (34). Thus, it has been suggested that regulatable promoters and vectors are required (35). Several systems for controlling exogenous transgene expression have been used including steroid hormones such as glucocorticoids (36). A limitation of using steroids is the interference of endogenous gene

Type of information to be remembered

Customs, the meanings of words, the colours and textures of objects, and how things smell. Most memory-impaired patients do not forget this kind of information, although they may have difficulty adding to their store of semantic knowledge. Amnesic patients are often unable, for example, to learn new words that enter the vocabulary after their neurological insult. Thus CW, an ex-patient of mine, cannot understand the terms 'AIDS' or 'e-mail', or 'mad cow disease', all of which came into widespread usage after 1985 when CW developed herpes simplex encephalitis.

Conditions that give rise to memory problems and typical presentations

Clients referred to rehabilitation centres for memory-therapy rehabilitation are most likely to have sustained a severe traumatic head injury, a cerebral vascular accident (CVA), herpes simplex encephalitis, or anoxic brain damage. It should also be remembered that these conditions are not mutually exclusive. I once saw a man who had a CVA while driving, thus sustaining some brain damage from the stroke he then crashed his car because of the CVA and sustained further brain damage from a head injury caused by the crash following this he stopped breathing for a while and appeared to sustain further damage from the anoxia then on top of everything else a haematoma developed and the man required surgery to remove the blood clot. Thus he sustained damage from four separate causes. He went on to respond reasonably well to rehabilitation and, although never able to return to work as a university lecturer, he became a secretary of his local Headway Group (The National Head Injuries...

Observance of Cytopathic Effect

A virus may kill an infected cell creating characteristic cytopathic damage or may replicate in cells without any visible effect. The type of changes induced by a virus can be significant for the type of virus and can be observed by the light microscope. The cytopathic effect (CPE) can be focal, diffuse through the cell monolayer, or at the edge of the culture. Cells may appear to be rounded or enlarged, growing in grapelike clusters, indicating adenovirus or herpes simplex virus. Influenza and mumps cause cells to fuse together, creating syncytia that detach from the surface. Cells may fuse and form multinucleated giant cells with granular cytoplasm typical of measles infection. Vaccinia and poxviruses create foci of fused cells, whereas picornaviruses induce proliferation of membranes in the cytoplasm and shrinkage of the nuclei (pyknosis). However, many viruses such as members of Bunyaviridae, Arenaviridae, and Retroviridae fail to produce obvious CPE and can replicate in culture...

The Role Of Viruses In Type B Adverse Drug Reactions

Evidence for the role of viruses first came from the observation that the use of ampicillin in patients with active EBV infection (i.e. infectious mononucleosis) results in a rash in 95 of patients (Sullivan and Shear, 2001). Another member of the herpes virus family, human herpes virus 6 (HHV6) has recently been implicated in hypersen-sitivity reactions associated with a number of drugs, including sulphasalazine (Suzuki et al., 1998 Descamps et al., 2001). However, whether this is a true predisposition or merely a coincidental factor needs further study. Perhaps the most striking association between viral infection and drug hypersensitivity has been observed in HIV-infected individuals. These patients have a higher frequency of hypersensitivity reactions with numerous anti-infective drugs including co-trimoxazole, sulphadiazine, dapsone, clindamycin, primaquine, and thioacetazone (Koopmans et al., 1995 Pirmohamed and Park, 2001b). This has been best shown with co-trimoxazole that is...

Unclassified Seizures

This similar syndrome presents later between 1-7 years of age. The response to anticonvulsant treatment and the degree of retardation is variable. The condition is associated with a large number of disorders including hypoxia, intracranial haemorrhage, toxoplasmosis, cytomegalovirus infection and tuberous sclerosis.

Engineering Novel Viruses Before and After Recombinant DNA

Derived by serial passaging in cell culture. Over the last 30 years, the recombinant DNA revolution has changed virology forever. Besides its impact on our ability to study specific viral nucleic acids and proteins, recombinant DNA technology (and PCR) sped up our ability to determine complete viral genomic sequences and create specific viral variants. The ability of scientists to engineer novel viruses varies greatly. Small positive-strand RNA viruses of bacteria, plants, and animals provided some of the first examples where infectious virus was produced via recombinant DNA. More recently, it has also become possible to engineer the > 29-kb RNA genome of coronaviruses and both monopartite and segmented negative-strand RNA viruses. Viruses in the family Reoviridae, with double-stranded RNA genomes, have proven more difficult. For herpesviruses, whose genomic DNA is infectious, the same technologies used for cloning large pieces of chromosomal DNA have been applied successfully to...

Cerebrospinal fluid analysis

As to differential diagnosis, Indian ink staining, cryptococcal antigen titres, and fungal culture can be decisive for the identification of cryptococcal meningitis. Other central nervous system opportunistic infections that can be identified by cerebrospinal fluid analysis include central nervous system tuberculosis, cytomegalovirus encephalitis, and neurosyphilis.

Strategies to Modulate Apoptosis TRAILR1 Monoclonal Antibody

INGN 201 is a replication incompetent adenovirus vector in which the E1 region has been replaced by wild-type p53 gene under the control of a cytomegalovirus promoter. Pre-clinical studies demonstrated anticancer properties in head and neck tumor cell lines and xenografts. A Phase I trial of stereotactic intratumoral injection of INGN 201 into recurrent glioma demonstrated minimal toxicity and the transfer of p53 to astrocytic tumor cells that led to transcriptionally active p53, with upregulation of target genes such as p21clp1 and apoptosis in subsets of cells. Phase II studies in patients with advanced recurrent squamous cell carcinoma of the head and neck treated with intralesional INGN 201 indicate that the virus is well tolerated.89 Disease stabilized in 6 of 17 patients with nonresectable disease, and 2 of 17 patients exhibited partial responses. Paradoxically, efficacy appeared independent of p53 status.

Amplification Method The Double Plasmid System

The pGS-MLC (Fig. 2) is based on the pGS-CMV, a generous gift from Dr. Sean M. Sullivan (University of Florida, Gainesville). pGS-CMV contains cytomegalovirus (CMV) enhancer promoter and a coding sequence for a chi-meric transcription factor (GAL4 p65) consisting of the yeast GAL4 DNA binding domain (amino acids 1-93) (2) and the human p65 activation domain (amino acids 283-551) (3) from nuclear factor kB (NF-kB). A 281-bp myosin light chain 2v promoter fragment was amplified by polymerase chain reaction (PCR) from pMLC-Luc (4) with primer pairs designed with 5' SbfI or 3' SacI sites on the ends. The PCR products were digested by SbfI and SacI and ligated to SbfI SacI-digested pGS-CMV plasmid to replace the CMV enhancer promoter. For an alternative way to obtain the fragment coding the GAL4 binding domain and the p65 activation domain, see Note 1.

Targeted Disruption of the PBR Gene in Steroidogenic Cells

Homologous recombination, in between the two PBR genomic DNA fragments and (ii) the Herpes Simplex Virus-tyrosine kinase gene, for the negative selection against cells that have randomly integrated the targeting construct, at the 3'-end of the second PBR genomic DNA fragment. The targeting vector was then transfected in R2C cells and selection was performed with G418 and ganciclovir (62). Four G418 Ganc-resistant cell lines were generated. PBR expression, examined by ligand binding, was absent in all four cell lines. In addition, the PBR-negative R2C cells produced minimal amounts (10 ) of steroids compared with normal R2C cells. However, incubation with the hydrosoluble analog of cholesterol, 22R-hydroxycholesterol, increased the steroid production by the PBR-negative R2C cells, indicating that the cholesterol-transport mechanism was impaired. The genomic DNA characterization of the PBR-negative R2C cells is under investigation.

Genetic Modification to Expressed Gene

By the use of suitably designed primers, many modifications can be made to the gene of interest. These may include the addition of restriction endonuclease (RE) sites to assist cloning into plas-mids, plus linker sequences of the appropriate length to ensure their restriction prior to cloning purification detection tags (if not included in the plasmid) and a terminal stop codon. In addition, the expression of human immunodeficiency virus Type 1 (HIV-1) IIIB gp120 and gp160 in both COS and Chinese hamster ovary (CHO) cells may be very poor unless the native signal sequence has been replaced by that from human tissue plasminogen activator (TPA) or herpes simplex virus (HSV) type 1 glycoprotein D (Chapman et al. 1991 Lasky et al. 1986). Berman et al. (1988b) highlighted the importance of the signal sequence in the optimal targeting of the recombinant protein to the cellular secretory machinery and hence to the ambient medium. This not only aids protein purification, but is also less...

Laboratory tests

Diagnosis of genital herpes requires the characteristic history and physical appearance of lesions plus the selective use of immunofluorescent assay Treatment of HSV Infections Acyclovir (Zovirax) 400 mg mg PO bid x 10 days Acyclovir (Zovirax) 5 mg kg IV q8h over one hour for 5-7 or until clinical resolution Acyclovir (Zovirax) 400 mg Acyclovir (Zovirax) 400 mg C. Acyclovir (Zovirax) is the drug of choice for the treatment and suppression of genital herpes. It is usually well tolerated, but nausea, vomiting, rash, or headache occur rarely. Topical acyclovir is not effective. Serious or life-threatening HSV infections require intravenous acyclovir. D. Other antivirals have more convenient bid dosing, but are more expensive than acyclovir and not more effective. A. Episodic acyclovir therapy. Early initiation of therapy has been shown to produce a reduction in the duration of symptoms. The patient should keep a supply of acyclovir and begin treatment at the earliest prodromal symptom.

Systemic nonhepatic infection and bacteremia

Hepatic involvement as just one component of a more generalized systemic infection occurs with some viruses (cytomegalovirus, Epstein-Barr virus), protozoa (Coxiella), parasites (malaria), and fungi (hepatosplenic candidiasis), particularly in immunosuppressed patients. Typhoid fever may cause an unusual hepatitis, but the jaundice in leptospirosis is due to hemolysis rather than hepatocellular injury.

Protective Features of an Intact HPA Axis and Glucocorticoid Response

Blockade of the HPA axis, either by adrenalecomy or hypophysectomy, or removal of functional GR by the antagonist RU486, has been shown to exacerbate disease course even to the extent of death in response to numerous bacterial or viral infections. Conversely, corticosterone replacement promotes survival and disease remittance. This was shown first in mice where adrenalectomy significantly reduced the lethal amount (LD50) of Escherichia coli serotype O111 B4 endotoxin (McCallum and Stith, 1982). In F334 N rats, treatment with RU486 and streptococcal cell walls (SCWs) resulted in higher mortality rates than SCW or RU486 alone (Sternberg et al., 1989a). Similarly, in LEW N rats, myelin basic protein (MBP)-induced experimental allergic encephalomyelitis (EAE) was exacerbated by adrenalectomy. Replacement of corticosterone, depending on dose used, either returned disease status to that of control animals or completely alleviated symptoms (MacPhee et al., 1989). Furthermore, intervention of...

Clinical Evaluation

The frequency of zoster increases markedly after age 55, but people of any age can be affected. Less than 5 of immunocompetent patients who have one episode of herpes zoster will have another, and the episodes are usually separated by years. HIV-infected patients are more likely to have recurrent herpes zoster infections.

Laboratory evaluation

The diagnosis of herpes zoster can be made on clinical grounds without the need for laboratory tests. Viral isolation and culture assays are not useful for varicella-zoster. 2. An isolated case of zoster in an apparently healthy young or middle-aged adult is probably not an indicator of an underlying immunodeficiency. HIV testing is considered when a patient who engages in high-risk behavior (sexual activities, drug use) develops zoster. Testing for HIV is also indicated when herpes zoster is protracted, recurrent, or involves multiple dermatomes.

Juxtaoral Organ of Chievitz

Herpes simplex is a common virus that often causes subclinical infections. It is, however, a cause of serious and sometimes fatal illnesses in immunocompromised patients. In the orofacial tissues, clinically apparent infections can be primary or recurrent. The majority of cases of oral infections are due to Herpes simplex type 1, but an increasing proportion is being attributed to Herpes simplex type 2, which is typically more closely associated with genital infections. The virus is transmitted by close contact. Although in the past primary herpes affected children most frequently, in Western societies it is seen increasingly in young and middle-aged adults. Primary herpes infection (primary herpetic gingivo-stomatitis) is characterised by widespread vesicular lesions of the oral mucosa 183 . Any site may be involved, but the hard palate and the dorsum of the tongue are the most common locations. The vesicles quickly rupture to leave shallow, painful, sharply demarcated ulcers that...

Antiviral therapy for zoster

Oral acyclovir does not have significant adverse effects nausea, headaches, diarrhea, and constipation may sometimes occur. c. IV acyclovir is reserved for the severely immunosuppressed (bone marrow transplant patients), disseminated infection, or ophthalmic zoster. 3. Famciclovir (Famvir) is equally effective as acyclovir it has a more convenient dosing interval one 500-mg tablet tid for 7 days. 4. Valacyclovir (Valtrex), may be slightly more effective than acyclovir 1,000 mg tid x 7 days 500 mg . 5. Foscarnet (Foscavir)is useful for acyclovir-resistant herpes infections. 6. Ophthalmic distribution zoster is a medical emergency which requires IV acyclovir and topical antivirals. A. PNH is the most common complication of herpes zoster. It is defined as chronic pain persisting for at least one month after the skin lesions have healed. B. The incidence of PHN after an episode of herpes zoster is 5-50 . Those aged 60 and older have a 50 chance of developing PHN....

Hand FootandMouth Disease

This is a common and usually mild viral infection that often causes local clusters of infections among groups of young children and is characterised by oral ulceration and a vesicular rash on the extremities. It is caused by a variety of strains of the coxsackie A16 virus and is highly infectious. Sporadic cases associated with Coxsackie A4-7, A9, A10, B1-B3, and B5 have also been reported. It frequently spreads through classrooms, schools and local communities in an epidemic manner. The incubation period is between 3 and 10 days. It presents clinically as small, scattered oral ulcers that often cause few symptoms. Although the initial lesions are vesicular, intact blisters are rarely seen. Unlike primary herpes infections, the gingivae are rarely affected. It is unusual for regional lymph nodes to be involved except in severe cases and constitutional symptoms tend to be mild or absent. The cutaneous exanthem consists of small vesicles or occasionally larger blisters that form mainly...

Other Considerations and Alternative Protocols

Choice of cells for fusion and selectable markers both donor and recipient cells must be exponentially growing before being harvested for fusion. In principle, cells between either different species or the same species can be fused with PEG, leading to the generation of interspecific or intraspecific hybrids. However, the fusibility varies depending on cell types. For example, it is much easier to fuse the mouse LA9 cells than it is the mouse E14 embryonic stem cells and the chicken DT40 cells. When fusion is performed between adherent and suspension cells, it is relatively easy to isolate hybrids of particular cell types if no efficient double positive selection is available. However, double positive selection usually is required to isolate hybrids if both donors and recipients in a fusion are suspension or adherent cells. Double selection requires donor and recipient cells to carry a different selectable marker respectively. A number of dominant markers are available for positive...

Role Of Nk Cells In Host Defense Against Disease

There have been increasing numbers of suggestions that NK cells may play some role in resistance against microbial infections. Most of the studies have been related to viruses 63 , with several investigators showing that cells infected by a variety of viruses become considerably more sensitive to lysis by NK cells 64,65 and persistently virus-infected tumour cells grow poorly in nude mice, apparently as a result of interferon induction and reactivity by NK cells 64 , Furthermore, resistance to infection by several types of viruses in vivo has been found to correlate with NK activity. There is considerable evidence for a role of NK cells in genetic resistance of mice to severe infection by herpes simplex virus type I 66 , A correlation has also been found between susceptibility to severe herpesvirus infections in patients and low NK activity against virus-infected target cells 67 , It also seems likely that NK cells play an important role in natural resistance to infection by mouse...

Differential Diagnosis

Predominantly an infection of sexually active individuals, usually observed in boys. Signs and symptoms include painful or burning urination and discharge from the urethral meatus. Causes may be gonococcal (Neisseria gonorrhea) and nongonococcal urethritis (NGU), which is now more frequent in the United States. NGU may be due to Chlamydia trachomatis, Ureaplasma urealyticum, and, less commonly, Trichomonas vaginalis or herpesvirus infection.

Further treatment of indolent lymphomas

Purine analogues fludarabine has a response rate of 70 (38 CRs) in untreated patients and 50 (15 CRs) in previously treated patients. Responses to cladribine are similar for previously treated patients but less in de novo treatment and responses are less durable. Neither convincingly improve disease free or overall survival. Fludarabine achieves responses in most patients with FL or SLL refractory to chlorambucil. Combinations of fludarabine with cyclophosphamide or with mitoxantrone (mitozantrone) and dexamethasone (FMD) increase response rates and are widely used. Prophylaxis of P carinii by cotrimoxazole in all patients and HZV by acyclovir in some is required during and for 6 months after therapy. Cellular blood products must be irradiated for 2 years after therapy.

Examination of the eye

Herpes labialis or a dermatomal vesicular eruption (suggestive of shingles) is indicative of a herpetic conjunctivitis. B. Purulent discharge suggests a bacterial infection. Stringy mucoid discharge suggests allergy. Clear watery discharge suggests viral infection. C. Ocular herpes simplex and herpes zoster is managed with topical agents, including trifluridine (Viroptic) and systemic acyclovir, famciclovir or valacyclovir.

Other Facial Nerve Disorders

Herpes zoster infection of the geniculate (facial) ganglion causes sudden severe facial weakness with a typical zoster vesicular eruption within the external auditory meatus. Pain is a major feature and may precede the facial weakness. Serosanguinous fluid may discharge from the ear. Antiviral agents (acyclovir) may help. HEMIFACIAL SPASM

Postoperative Management

It is imperative to maintain prophylaxis for cytomegalovirus (CMV) and Epstein Barr, virus (EBV) infections post operatively particularly where the donor is positive for CMV or EBV and the recipient is negative. CMV prophylaxis is best accomplished with Gancyclovir, although CMV immune globulin (Cytogam) has also been used. Acyclovir, which is less effective than Gancyclovir for CMV, is effective prophylaxis for EBV. Intravenous immune globulin (IVIG) is also used by some centers as EBV prophylaxis.

Antifungal Oligonucleotides

Targeting RNA with oligonucleotides is emerging as an important therapeutic strategy to treat certain forms of cancer and some infectious states (Disney et al., 2001 Testa et al., 1999). The antisense oligonucleotide Vitravene (Galderisi et al., 1999), has proven to be effective in treating cytomegalovirus retinitis in AIDS patients intolerant, unresponsive or have contraindications to other treatment(s) of the infection. Gentasense, anti-bcl-2 anti-sense messenger RNA construct, and other oligonucleotide preparations (Childs et al., 2002) are proven potent against acute myeloid leukemia. Features that influence oligonucleotide affinity to bind target RNA and its nuclease stability can be accommodated into the sequence design (Freier & Altman, 1997). Recent evidence suggest that C. albicans takes up significant quantities of oligonucleotides in an energy-dependent manner, taken up oligonucleotides remain stable for > 12 h (Disney et al., 2003). A 19-mer with a 2'-O-methyl...

The importance of early diagnosis

Institution of antiviral therapy with acyclovir (aciclovir) can dramatically reduce the mortality and morbidity associated with herpes simplex encephalitis, but only if started early. The prognosis is poor once the patient with this typically rapidly progressing infection reaches the stage of stupor and coma. Therefore there is an abundant literature focusing on the early diagnosis of herpes simplex encephalitis. Typical clinical presentation includes signs and symptoms of focal neurological impairment or personality change in the setting of an acute or subacute febrile illness. However, focal neurological abnormalities such as partial seizures or hemiparesis do not occur in a majority of patients, and lateralized signs may be subtle and or transitory. Fever, head or neck pain, and altered mentation are almost invariably present however, these features are non-specific, and very early in its course herpes simplex encephalitis may be indistinguishable from common viral infections with...

Supportive management

Although early delivery of acyclovir results in improved outcome from herpes simplex encephalitis, morbidity and mortality remain high. Patients who present for medical attention with stupor or coma have a mortality rate of approximately 25 per cent and a very poor prognosis for good functional recovery whether or not acyclovir is administered. A substantial number of these individuals succumb to secondary brain injury. Factors likely to produce additional morbidity by secondary injury mechanisms include severe cerebral edema with attendant elevation of intracranial pressure (ICP), incarceration of major vessels (e.g. posterior cerebral artery at the tentorial hiatus), and compromised oxygen delivery to the brain secondary to hemodynamic and or pulmonary dysfunction. A consistent program of medical management aimed at reducing secondary injury may improve an individual's chances of good functional recovery. In addition to the foundations of supportive care necessary for any critically...

Airway and ventilatory management

Agitation and disordered ventilation secondary to bilateral cerebral or brainstem involvement (particularly Cheyne-Stokes respiration, episodic hyperventilation) are common in viral encephalitis, particularly herpes simplex encephalitis and rabies. However, pharmacological suppression of abnormal breathing patterns or behavior should not generally not be practised unless there is compromised gas exchange or increased work of breathing represents a significant physiological stress in an individual patient. Too liberal use of sedatives will obviously result in sacrifice of the neurological examination and should be undertaken only with appropriate justification, and then with caution. In non-intubated patents with severe agitation that threatens patient safety or the provision of care, short-term use of haloperidol, administered intravenously, is a particularly useful strategy because this agent generally does not suppress respiratory drive and has little adverse effect on hemodynamics.


An electroencephalogram is a non-invasive, harmless, and inexpensive investigational technique. It is mainly used to show epileptic activity. It may also help to differentiate some causes of impaired consciousness and coma. It can help to distinguish the effects of metabolic and toxic changes from cerebral hypoxia, encephalitis, and in some cases subclinical epilepsy. It also reveals characteristic features in conditions such as herpes encephalitis. It may be used to give prognostic information in suspected ischemic damage or head injury. It may also help to differentiate locked-in syndrome from persistent vegetative state.

Radiographic and Other Studies

Infants, especially those who are younger than 1 month or who appear ill, require thorough evaluation with blood culture, urine evaluation and culture, and cerebrospinal fluid (CSF) evaluation with culture and appropriate CSF polymerase chain reaction (eg, herpes, enterovirus). 2. Admission and empiric treatment to cover group B Streptococcus, Listeria monocytogenes, and gram-negative enteric organisms is warranted, as well as consideration of empiric treatment of herpesvirus with acyclovir. A third-generation parenteral cephalosporin or an aminoglycoside (usually gentamicin) coupled with ampicillin is the current treatment of choice in most settings. Clinician must still rule out meningitis in this patient.

Allogeneic stem cell transplantation

Allogeneic stem cell transplantation, using myeloablative doses of chemotherapy and or radiation followed by infusion of allogeneic stem cells, remains the only proven curative therapy for CML. Stem cells used for allogeneic transplantation may be obtained from either the bone marrow or the peripheral blood of the donor. Allogeneic stem cell transplantation in CML has a long-term survival rate of 55-80 , with median survival of more than 10 years for patients transplanted during chronic phase with non-T-cell-depleted marrow, using modern GVHD and cytomegalovirus prophylaxis. Results with allogeneic stem cell transplantation are much better for patients in chronic-phase CML than for those in the accelerated or blastic phase of the disease. Long-term overall survival rates are 15-20 for patients transplanted during the accelerated phase and below 10 for patients transplanted during the blastic phase.

Clinical Evidence Of Enteroviral Infection In Cardiomyopathy

Viral infection has been clearly associated with acute episodes of myocarditis in which a patient often presents with cardiomyopathy and heart failure. Many different infectious agents have been considered as the cause of viral myocarditis, including enteroviruses, adenovirus, cytomegalovirus,3'4 hepatitis C virus,5 and others. Among the most commonly identified infectious agents are the CVBs, members of the enterovirus genus of the picornavirus family. Reports of isolation of coxsackievirus from the heart or pericardial fluid of patients with acute myocarditis date back as far as 1965,6J with numerous reports since of virus isolated from the heart or pericardial fluid or demonstrating the presence of viral antigens in diseased heart tissue.7-14 According to World Health Organization surveys from many different countries, 34.6 per 1,000 of all CVB infections are associated with cardiovascular disease.15

Overexpression of nNOS by the Adenovirus Vector

The rat nNOS cDNA was cloned into a pGEM CMV plasmid. This plasmid was modified and digested into a linearized fragment containing the left Ad5 inverted terminal repeat (ITR), cytomegalovirus (CMV) promotor, nNOS cDNA, and simian virus 40 (SV40) pA. The vector backbone DNA was a fragment with an ITR and the viral packaging signal at the extreme 5' end, which was prepared from the parent vector Ad.p-gal. These two fragments were ligated for 1 h at room temperature using T4 DNA ligase. The ligated DNA was transfected into 293 cells using the calcium phosphate method. Following the observation of a cytopathic effect, the recombinant Ad.nNOS was isolated and purified by double cesium chloride density cen-trifugation, as previously described (20,21). This recombinant Ad.nNOS vector contains a rat nNOS cDNA under the control of the CMV immediate-early promoter. The vector expresses functional nNOS protein in human vascular smooth muscle cells and human umbilical...

Opportunistic Infections in HIV Infected Patients

-Acyclovir (Zovirax), 200-400 mg PO 5 times a day for 10 days, or 5 mg kg IV q8h OR in cases of acyclovir resistance, foscarnet, 40 mg kg IV q8h for 21 days. Herpes Simplex Encephalitis (or visceral disease) -Acyclovir 10 mg kg IV q8h for 10-21 days. Herpes Varicella Zoster -Acyclovir 10 mg kg IV over 60 min q8h for 7-14 days OR 800 mg PO 5 times d for 7-10 days OR -Famciclovir (Famvir) 500 mg PO q8h for 7 days 500 mg OR -Valacyclovir (Valtrex) 1000 mg PO q8h for 7 days 500 mg OR -Foscarnet (Foscavir) 40 mg kg IV q8h. Cytomegalovirus Retinitis for 14-21 days OR -Foscarnet (Foscavir) 60 mg kg IV q8h for 2-3 weeks OR -Cidofovir (Vistide) 5 mg kg IV over 60 min q week for 2 weeks. Administer probenecid, 2 g PO 3 hours prior to cidofovir, 1 g PO 2 hours after, and 1 g PO 8 hours after. Suppressive Treatment for Cytomegalovirus Retinitis -Ganciclovir 5 mg kg qd. -Foscarnet (Foscavir) 90-120 mg IV qd OR

S Evidence statements Steroids

The effectiveness of steroids in the long-term treatment of MS was investigated in one systematic review (Ia), six RCTs (Ib) and one CCT (IIa). The review117 included four placebo-controlled RCTs comparing the effects of ACTH (n 1), prednisolone (n 1) and methyl-prednisolone (n 2) given for 9-18 months. It reported no significant effect on long-term functional improvement or on relapse occurrence. The review also reported the occurrence of both major and minor side effects including herpes simplex, herpes zoster, severe ankle oedema, femur fracture, acute anxiety and severe depression.117 Four of the controlled trials also compared steroids to placebo. Two RCTs, one of ACTH and the other of two different doses of zinc hydroxide corticotrophin, found no effect of treatment on any of the outcomes investigated.142,143 One reported a greater incidence of adverse effects including steroid diabetes, increased blood pressure, oedema, acne and hirsutism in the intervention groups.142 A...

Immunocompetent Patient

Therapy with oral acyclovir is not recommended routinely for the treatment of uncomplicated varicella in the otherwise healthy child < 12 years of age. B. Oral acyclovir may be given within 24 hours of the onset of rash. Administration results in a modest decrease in the duration and magnitude of fever and a decrease in the number and duration of skin lesions. C. Acyclovir (Zovirax) 80 mg kg day PO q6h for five days, max 3200 mg day cap 200 mg susp 200 mg 5 mL tabs 400, 800 mg

Was the substance truly blood Was it the patients blood

Can result from gastroesophageal reflux disease (GERD). Children with bleeding esophagitis as a result of GERD are more likely to have a neuromuscular disease or hiatal hernia. Other causes of esophagitis include mechanical injury by a foreign body, chemical injury from caustic ingestion, medication (pill esophagitis), or infection (Candida albicans, Aspergillus, herpes simplex virus, cytomegalovirus).

Personality change due to cerebral disease

Irritability and aggressive outbursts are especially associated with temporal lobe pathology. Herpes simplex encephalitis has an affinity for the temporal lobes, so behavioural manifestations are common during the acute stages of the illness and after recovery if there is residual brain damage. Patients who survive temporal lobe damage may manifest the features of the KlUver-Bucy syndrome which include hypersexuality, aggressive outbursts, excessive oral behaviour, and visual agnosia.

Psychological Stress and Immunity

Although studies in humans have established a clear relationship between stress and susceptibility to HSV infection, these studies have not been able to address each of the components of the immune response that underlie this relationship. However, the use of animal models has provided the opportunity to determine these immune components given the ability to establish an HSV infection and assess the responses at various sites throughout the body. Using a murine model, the effects of stress on susceptibility to HSV infections have been known for nearly 50 years (Rasmussen et al., 1957). Although these studies were important in establishing an association between stress and viral infection, they were unable to identify specific antiviral immune defense mechanisms that were modulated by stress and that contributed to viral pathogenesis, because the

Inflammatory Response

An inflammatory response to many pathogens is generally characterized by redness, swelling, heat, and pain at the site of infection. These symptoms depend on a constellation of events including, but not limited to, proin-flammatory cytokines (e.g., IL-1, IL-6, tumor necrosis factor-a), and leukocyte trafficking. There have been numerous studies that have examined the influence of psychological stress on the early, inflammatory events that are initiated upon HSV infection. For example, using a murine model, restraint stress was shown to decrease both type I and II interferon production in response to a primary, HSV-1 dermal infection (Ortiz et al., 2003). Furthermore, this decrease in interferon production correlated with an increase in virus titer at the site of primary infection. In another study, hyperther-mic stress was shown to increase the levels of both IL-6 mRNA and the protein itself in the trigeminal ganglia of HSV-1 latently infected mice (Noisakran et al., 1998).The...

Ocular Barriers To Various Routes Of Administration

The only possible way to achieve therapeutic concentrations in the posterior segment of the eye was found to be the intravitreal administration (43-51). This route of administration has become the recommended therapy for the treatment of endophthalmitis and cytomegalovirus retinitis. Drugs injected into the vitreous may be eliminated by two routes. Drugs eliminated by diffusion into the posterior chamber with subsequent removal by normal egress of fluid from the anterior chamber (52,53) generally exhibit half-lives within a range of 20-30 hours (53). The second route is through the retina via penetration of the blood-retinal barrier (52,53). Drugs eliminated by this route usually exhibit half-lives in the range of 5-10 hour (53).

Leukocyte Trafficking and Recruitment

Leukocyte recruitment to sites of inflammation is crucial for initiating immune-mediated control of a viral infection. An inhibition of leukocyte trafficking may impair the ability of the immune system to control viral replication, thus leading to an increase in the pathology associated with viral replication. Restraint stress has been shown to alter the pattern of leukocyte recruitment and retention. For example, during a primary intranasal HSV infection, restraint stress delays both CD4+ and CD8+ T-cell recruitment into the brain of mice with symptoms of HSV encephalitis (Anglen et al., 2003). In a corneal infection model, hyperthermic stress was found to reduce the numbers of NK cells in the trigeminal ganglia of mice that were latently infected with HSV-1 (Noisakran et al., 1998). Restraint stress was found to suppress lymphadenopathy in HSV-1 infected mice. This suppression was glucocorticoid dependent as receptor blockade with the glucocor-ticoid receptor antagonist RU486...

Minor group antigens also may uncommonly contribute to

Hemolytic anemias, transfusions, and trauma associated with hematomas result in increased bilirubin load and are causes of indirect hyperbilirubinemia in any age group. Infants with galactosemia and hypothyroidism may present initially with indirect hyperbilirubinemia in the newborn period. Congenital infections (eg, cytomegalovirus, toxoplasmosis) that cause systemic illness may be associated with hemolysis and indirect hyperbilirubinemia, in addition to hepatitis and direct hyperbiliru-binemia. Indirect hyperbilirubinemia may be exaggerated in the presence of the following risk factors Asian or Native American race, prematurity, polycythemia, male sex, Down syndrome, oxytocin induction, delayed stooling, and having a sibling with a history of neonatal jaundice.

Expression Vectors 5221 Plasmid vectors

Cho Protein Production

Map of plasmid pEE14, an expression vector for CHO cells. GS hamster glutamine sythetase minigene (contains a single GS intron expressed from the SV40 late promoter (SV40l) hCMV-MIE human cytomegalovirus major intermediate early enhancer-promoter MCS multiple cloning site Apr ampicillin resistance gene poly A polyadenylation signal Map of plasmid pEE14, an expression vector for CHO cells. GS hamster glutamine sythetase minigene (contains a single GS intron expressed from the SV40 late promoter (SV40l) hCMV-MIE human cytomegalovirus major intermediate early enhancer-promoter MCS multiple cloning site Apr ampicillin resistance gene poly A polyadenylation signal The most generic and versatile promoter enhancer assemblies for mammalian expression are derived from viral systems. The human cytomegalovirus major immediate-early viral promoter enhancer (hCMV), the Rous sarcoma virus long terminal repeat promoter (RSV-LTR), the simian virus early promoter enhancer (SV40), and the human...

Cells of the Innate Immune System

The nonspecific innate immune response to a viral infection consists of a variety of different cell types that contribute to the early defense against infection. To date, only a few studies have examined the influence of stress on these cell types in the context of an HSV infection. Macrophages produce cytokines that influence the adaptive immune response, may present antigen to B and T lymphocytes, and eliminate virus infected cells. The role of macrophages during a primary HSV infection is not completely understood. However, both adoptive transfer and depletion studies have shown that macrophages can indeed contribute to host resistance to an HSV infection (Morahan and Morse, 1979 Pinto et al., 1997). In an ex vivo activation assay, Koff and Dunegan (1986) demonstrated that the sympathetic nervous system products epinephrine and norepinephrine can reduce the ability of macrophages to lyse HSV-1-infected target cells. In support of these in vitro findings, Davis and colleagues have...

Prevention And Treatment

Several kinds of antiviral drugs interfere with viral nucleic acid synthesis. Unfortunately, the number of antiviral drugs is small compared to that of drugs that treat bacterial, fungal, and parasitic infections. Because viruses use host cells in their life cycles, it is difficult to design a drug that blocks the virus but doesn't harm cells. The drug acyclovir (ay-SIE-kloh-viR) blocks the DNA polymerase of herpes viruses and chickenpox virus. Such drugs do not destroy a given virus but allow time for the body to build up an immune response to the virus.

Detection Of Viral Genomes In The Heart By Rtpcr

In the last decade, another highly sensitive technique, the PCR, has become the most commonly used method for the detection of viral DNA and RNA sequences in the heart of patients with myocarditis and DCM. Primarily as a result of the identification of different viral nucleic acids in the myocardium of these patients by PCR, it is widely thought that myocarditis can develop as a result of infection with enteroviruses,4 adenoviruses,5'6 cytomegalovirus,6'9 Epstein-Barr virus,12 herpes simplex virus,6 human herpesvirus-6,13 HIV,14 influenza A and influenza B virus,18 PVB19,15-17 or hepatitis C virus.21,22 Martin et al.5 reported in a PCR analysis of children with acute myocarditis that viral sequences were present in 26 of 38 myocardial samples (68 ) 8 enterovirus, 15 adenovirus, 2 herpes simplex virus, and 1 cytomegalovirus. In addition, PCR analysis of endomyocardial biopsy specimens suggests that fibroelastosis is a sequela of viral myocarditis after infection with mumps virus (>...

Use of granulocyte transfusion

Although granulocyte transfusion has been available for many years, its use has waned over the past decade, partly because of advances in antimicrobial therapy and the availability of hemopoietic growth factors. In addition, early studies showed that no clinical benefit was demonstrated, primarily because the collection method prevented sufficient numbers of granulocytes from being collected, thus requiring frequent transfusions, and the function of the cells collected was defective. There have also been concerns regarding the risk of cytomegalovirus infections, transfusion-associated graft versus host disease, and the development of acute respiratory distress syndrome following transfusion of granulocytes. Efforts to improve granulocyte collection following granulocyte colony-stimulating factor administration to donors is now being considered. The use of granulocyte colony-stimulating factor offers many potential advantages. Its ability to increase granulocyte numbers would allow...

Treatment of nonbacterial infections

Viral infections such as herpes simplex, varicella zoster, cytomegalovirus, and adenoviruses frequently occur in neutropenic patients, particularly those with impaired cell-mediated immunity. These infections can be primary, for example when a renal transplant patient who is seronegative for cytomegalovirus is grafted with a kidney from a seropositive donor. More often they result from reactivation of latent virus, as when a patient with Hodgkin's disease develops varicella zoster following irradiation or chemotherapy. Herpes simplex virus infection usually presents as a mucocutaneous infection which is easy to diagnose except in patients with mucocutaneous bleeding. Acyclovir (aciclovir) is the treatment of choice and is relatively free from toxicity as it can only be converted into its active form by herpes viruses and not by the host cells. It is excreted by the kidneys and the dose should be reduced according to creatinine clearance. Because of poor bioavailability of orally...

Genes whose products are induced rapidly and transiently in response to extracellular stimulation

The term immediate early gene (IEG) was borrowed from virology. During the infectious cycle, the viral proteins are expressed in an orderly programme, which involves immediate early, delayed early, and late proteins (Honess and Roizman 1974 Weinheimer and McKnight 1987). For example, in the virus Herpes simplex, products of IEGs are detectable at 1 h of infection, of delayed early genes at 3 h, and of late response genes at 6-7h (Weinheimer and McKnight 1987). Each phase in the cascade is required for the initiation of the next phase. An analogous picture was later unveiled in the response of mammalian cells to extracellular stimuli (Nathans et al. 1988 Lanahan et al. 1992). The modified expression of cellular IEGs is detected within minutes of the extracellular stimulation, and commonly lasts only for a short time (e.g. tens of minutes Sheng and Greenberg 1990).

Viral Diseases Hivaids

Toxoplasma encephalitis Cryptococcal meningitis Cytomegalovirus encephalitis polyradiculitis Progressive multifocal leukoencephalopathy Primary central nervous system lymphoma The worldwide use of highly active antiretroviral therapy (HAART) has played an important role in changing the incidence of neurological complications in AIDS patients. Recent studies have shown that HAART has produced both quantitative and qualitative changes in the pattern of HIV neuropathology an overall decrease in the incidence of some cerebral opportunistic infections such as toxoplasmosis and cytomegalovirus encephalitis, for which successful treatment is available, whereas other uncommon types and new variants of brain infections, such as varicella-zoster encephalitis, herpes simplex virus encephalitis or HIV encephalitis, are being reported more frequently as ART promotes some immune recovery and increases survival (8). In developing countries, some endemic infections such as tuberculosis and Chagas...

Preliminary Preparations

The dilutions and volumes of drug needed to perform a susceptibility test are dependent on the range of drug concentrations employed and the total number of HSV isolates to be tested. Figures 3 and 4 illustrate the typical ranges of acyclovir and foscarnet, respectively, employed in the HSV hybridization assay and the configurations of the 24-well plates when one clinical HSV isolate and two control virus strains are examined. Figure 3 Illustration of the typical ranges of acyclovir ( ng ml) employed in the HSV hybridization assay, and the configuration of the 24-well plates when two control virus strains (A) and one clinical HSV isolate (B) are examined. Figure 3 Illustration of the typical ranges of acyclovir ( ng ml) employed in the HSV hybridization assay, and the configuration of the 24-well plates when two control virus strains (A) and one clinical HSV isolate (B) are examined.

Box 351 Causes of viral encephalitis

Herpes simplex virus (HSV-1, HSV-2) Other herpes viruses > cytomegalovirus (CMV) > human herpes virus 6 (HHV6) Adenoviruses Patients with viral encephalitis are marked by acute onset of a febrile illness and can experience signs and symptoms of meningeal irritation, focal neurological signs, seizures, alteration of consciousness and behavioural and speech disturbances. The diagnosis is made by immunological tests, neuroimaging techniques, electroencephalography and, sometimes, brain biopsy. No specific treatment is available for every encephalitis, and the illness often requires only medical support. The mortality rate and severity of sequelae depend largely on the etiological agent. Herpes virus encephalitis carries a mortality rate of 70 in untreated patients, with severe sequelae among survivors. Pharmacotherapy for herpes virus encephalitis consists of acyclovir and vidarabine. Effective preventive measures include control of vectors by removing water-holding containers and...

Inhibition of viral DNA polymerases by substrate analogs

Because DNA polymerases play central roles in DNA replication, inhibition of viral DNA polymerases should slow down or stop viral infections. Most of the approved antiviral inhibitors are nucleoside analogs. They are chain terminators like AZT lacking the 3'-hydroxyl group, or are acyclic without a deoxyribose like acyclovir. These drugs are reviewed in detail in Chapter 11 in this book. Because pyrophosphate is a product formed during nucle- otide incorporation, its analog could bind to and inhibit DNA polymerases. Phosphonoformic acid or Foscarnet (Figure 6.6), a pyrophosphate analog, is an antiherpes drug that binds to the site normally occupied by pyrophosphate and inhibits the catalytic cycle of a herpes DNA polymerase.117

Limitations of the Procedure

Antiviral susceptibility testing appears to be indicated for patients in whom resistance tends to appear the most. These patients normally include immunocompromised individuals, especially transplant recipients and AIDS patients previously treated with anti-HSV agents (Table 3). One report suggests recurrent acyclovir-resistant HSV infection in an immunocompetent individual (Kost et al., 1993) which correlated with clinical failure of antiviral therapy. 3. Resistance of HSV isolates to acyclovir is becoming more commonplace, occuring at rates of 2-14 in the immunocompromised host (Wade et al. 1983 Englund et al., 1990). In these patients, resistant HSV can be associated with severe progressive disease that does not respond to antiviral treatement (Bean et al., 1987 Norris et al., 1988 Erlich et al., 1989a Sacks et al., 1989 Gateley et al., 1990 Ljungman et al., 1990). 5. Antiviral susceptibility testing may become useful in choosing between continuous high-dose acyclovir and foscarnet...

Transient Transgene Expression

The most powerful promoter allowing expression in all cell types is probably the immediate early promoter and enhancer of human cytomegalovirus, CMV (11). This promoter fused to lacZ drives expression in most tissues of the zebrafish embryo (12). Gibbs et al. (13) compared the CMV promoter with the SV-40 early promoter and the RSV-LTR promoter, each fused to the luciferase gene. The CMV promoter gave the strongest signal with the lowest concentration of luciferase reaction components, allowing positive fish to be raised to adulthood.

Immunosuppression and AIDS

Similar arguments for early 'blind' anti-infective therapy apply in patients immunosuppressed for other reasons, such as transplant recipients or those receiving steroid therapy. Transplant recipients often have impaired cell-mediated immunity and may be more susceptible to fungal, protozoal, or viral infection in addition to bacterial sepsis. A variety of opportunistic infections, such as Pneumocystis carinii pneumonia, cytomegalovirus infection, or Mycobacterium intracellulare avium infection, may cause fever in patients with AIDS, and these require investigation and treatment.

Antibacterial or Antiviral Efficacy

Patients undergoing penetrating kerato-plasty wore a presoaked collagen shield for at least 30 minutes preopera-tively. Control patients received drops of TFT only. Cornea and aqueous samples were obtained during surgery. Collagen shields did not enhance delivery of TFT to the cornea with an intact epithelium. In corneas with poor epithelium, drug penetration was higher but variable. They concluded that the role of collagen shields as a drug delivery system for the treatment of herpes simplex keratitis remains to be determined.

What Is The Problem With Current Diagnostic Techniques For Myocarditis

The ongoing European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID) has expanded the light microscopic Dallas criteria for myocarditis by including immunohistochemical variables of myocardial inflammation.7 Endomyocardial biopsy specimens are screened not only for infiltrating cells but also for the presence of persisting viral genome (enterovirus, cytomegalovirus, and adenovirus). This method shows inflammatory processes in the heart in 17.2 of the 3,055 patients screened. Only 182 of these patients showed a reduced ejection fraction below 45 , fulfilling the entrance criteria for the ESETCID trial. These data indicate that, in symptomatic patients, myocarditis should always be considered and relatively well-preserved left ventricular function does not exclude the diagnosis. In the ESETCID trial, viral genome was detected in 11.8 of patients (enterovirus 2.2 , cytomegalovirus 5.4 , adenovirus 4.2 ).

Lysogeny or Latency by Integration

The bacterial virus lambda (l), which infects the bacterium E. coli, recognizes and integrates into a special sequence of DNA on the chromosome of its host cell, known as attl (l attachment site). Integration occurs by site-specific recombination as described in Ch. 14. This allows lambda to occasionally pick up and carry bacterial genes as described in the chapter on bacterial genetics (Ch. 18). Some animal viruses, such as the herpes viruses, also insert themselves into the chromosomes of their host cells. Some have special recognition sites, while others insert at random. Retroviruses,