European guideline for the management of genital herpes.
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Biomedical subjects
Publications and source records attributed to P Woolley.
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The prevalence of genital herpes is increasing in several populations worldwide. Factors that may be contributing to this increase include greater numbers of sexual partners, the high frequency of asymptomatic infections, poor use of safe sexual practices, and possibly the decreased incidence of childhood oral herpes simplex virus infection. Transmission occurs via skin-to-skin or mucous membrane contact during periods of viral shedding when lesions are present but may also occur when the patient is unaware of the lesions or when lesions are not clinically apparent. This has important implications for strategies to prevent transmission of the disease. The introduction of the antiherpes agent, acyclovir, and more recently famciclovir and valacyclovir, facilitates the management of genital herpes. Treatment of first-episode genital herpes reduces the severity and duration of symptoms, time to lesion healing, and cessation of viral shedding. Episodic treatment of recurrences as they occur may be of benefit to some patients. Daily suppressive therapy significantly reduces the frequency of recurrences and asymptomatic viral shedding. Accordingly, patients who experience frequent or severe recurrences, those particularly troubled by their disease, and those who wish to reduce the frequency of asymptomatic infection generally prefer suppressive therapy. The possibility that suppressive therapy may have an impact on transmission of the disease is currently under investigation. Antiviral treatments have important implications for public health and may help reduce the psychological and psychosocial impact of genital herpes on individual patients.
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Determining how antibiotics inhibit ribosomal activity requires a detailed understanding of the interactions and relative movement of tRNA, mRNA and the ribosome. Recent models for the formation of hybrid tRNA binding sites during the elongation cycle have provided a basis for re-evaluating earlier experimental data and, especially, those relevant to substrate movements through the peptidyl transferase centre. With the exception of deacylated tRNA, which binds at the E-site, ribosomal interactions of the 3'-ends of the tRNA substrates generate only a small part of the total free energy of tRNA-ribosome binding. Nevertheless, these relatively weak interactions determine the unidirectional movement of tRNAs through the ribosome and, moreover, they appear to be particularly susceptible to perturbation by antibiotics. Here we summarise current ideas relating particularly to the movement of the 3'-ends of tRNA through the ribosome and consider possible inhibitory mechanisms of the peptidyl transferase antibiotics.
OBJECTIVE: To determine the efficacy and safety of once daily valaciclovir for the suppression of recurrent genital herpes simplex virus (HSV) infection in immunocompetent patients. METHODS: 382 otherwise healthy patients with a history of frequently recurring genital HSV infection (eight recurrences per year) were randomly allocated to receive either oral valaciclovir (500 mg once daily) or placebo (3:1 ratio) for 16 weeks or until the first genital HSV recurrence, whichever occurred first. Patients were clinically assessed at regular intervals and also if they experienced a recurrence. Safety was evaluated through adverse experience reporting and monitoring of haematology and biochemistry variables. On completion of the double blind phase, patients were eligible for follow up to a maximum of 48 weeks' treatment with open label valaciclovir (500 mg once daily) for further safety monitoring. The results from the double blind phase of the study are reported here. RESULTS: A significant difference was detected between valaciclovir and placebo in the time to first recurrence of genital HSV infection. The hazard ratio [95% confidence interval] for valaciclovir v placebo was 0.155 [0.112, 0.214], p < 0.0001. Valaciclovir prevented or delayed 85% of the recurrences that would have occurred with placebo. After 16 weeks (day 112) with treatment, 69% of patients receiving valaciclovir were recurrence free compared with only 9.5% of patients assigned to placebo. The safety profiles of valaciclovir and placebo were comparable, with adverse experiences being infrequent and generally mild. CONCLUSION: This study has demonstrated that once daily valaciclovir (500 mg), is highly effective and well tolerated for the suppression of recurrent genital HSV infection. Once daily dosing with valaciclovir provides a more convenient dosing regimen than the more frequent aciclovir regimens.
Genital herpes, usually caused by herpes simplex virus type 2 (HSV-2), is the most common cause of genital ulceration. The primary episode of genital herpes is generally the most painful. Subsequent recurrences are generally milder and localized. Diagnosis is made clinically, but should be confirmed by culture or serology. Management includes antiviral drug therapy--acyclovir, valacyclovir, or famciclovir--as well as analgesics. In addition, patient counseling and education are vital. Antiviral treatment decreases the severity and duration of primary genital herpes and of recurrences, and it may be used as a continuous suppressive therapy to decrease the incidence of recurrence. Pregnant women who have a history of genital herpes or recent primary infection should deliver by cesarean section in the presence of genital lesions at labor or primary HSV infection at any time during the third trimester to prevent transmission to the neonate. Part 1, "Genital Herpes: Recognizing the Problem," addresses the problems involved in diagnosing the infection and quantifying the epidemic.
Genital herpes, usually the result of an infection with herpes simplex virus type 2 (HSV-2), is the most common cause of genital ulceration. The first clinical episode is called primary genital herpes; recurrent HSV infection occurs in up to 80% of patients. Because not every individual who acquires the virus develops symptoms, it is difficult to estimate the prevalence of HSV infection. Transmission of virus occurs not only in the presence of apparent lesions, but asymptomatic viral shedding can also spread infection in the absence of lesions. The primary episode of genital herpes is generally the most painful, characterized by multiple and bilateral lesions and associated with tender inguinal lymphadenopathy as well as systemic symptoms. Subsequent recurrences are generally milder and localized. Diagnosis is made clinically, but should be confirmed by culture or serology. Part 2, "Genital Herpes: Treatment Guidelines," addresses aspects of treatment, including special considerations in treating pregnant women.
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This essay is an attempt to point up the gap between, on the one hand, the methods currently available to the biologist in the laboratory and, on the other, the kind of data that he or she would need in order to characterise genetically engineered proteins of topical biological interest in such a way as to make use of the techniques of protein engineering.