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PubMed2002

Valacyclovir in the treatment of genital herpes and herpes zoster.

Genital herpes is prevalent and sometimes debilitating. Likewise, herpes zoster ('shingles') can be painful and often disabling. The treatment of these conditions has been advanced over the past two decades by the introduction of guanosine nucleoside antivirals such as valacyclovir (Valtrex), Glaxo Wellcome), the highly bioavailable prodrug of acyclovir (Zovirax), Glaxo Wellcome). This review describes the pharmacology, pharmacokinetics, clinical efficacy and tolerability of valacyclovir and considers its clinical attributes in the context of those of the antivirals, acyclovir and famciclovir (Famvir), SmithKline Beecham). The data demonstrate that valacyclovir is more effective than placebo and as effective as other antivirals in the episodic and suppressive treatment of recurrent genital herpes. Valacyclovir is the only antiviral shown to be effective with a short (3-day) course in the episodic treatment of recurrent genital herpes, as well as with once-daily dosing for daily suppressive therapy. In herpes zoster, valacyclovir is as effective as famciclovir and more effective than either placebo or acyclovir at facilitating cutaneous healing and healing of zoster-associated pain and post-herpetic neuralgia. Valacyclovir is well tolerated, with convenient dosing frequencies for the treatment of genital herpes or herpes zoster, it also has the option for use as a short course therapy in the episodic treatment of recurrent genital herpes, all of which are important benefits in the management of these conditions.

Acyclovir↗
PubMed1993

Influence of steroid hormones on 5 alpha-reductase activity in female and male genital skin fibroblasts in culture.

The physiological regulation of 5 alpha-reductase (5 alpha R) as well as the complex pathogenesis of male and female androgenic disorders are still incompletely understood. Therefore, we examined the influence of various steroid hormones on the 5 alpha R activity in female and male genital skin fibroblasts in primary culture to test whether the 5 alpha R activity is identically regulated in genital skin samples of both sexes. Nine foreskin samples of male patients and 11 specimens of female genital skin were prepared and cultured as primary tissue cultures. After pre-incubation with various unlabeled steroids, [3H]-testosterone was added to the cultures and the 5 alpha R activity (conversion of testosterone to dihydrotestosterone) measured. (a) The pre-incubation of male foreskin fibroblasts with unlabeled androstenedione and androstandione both resulted in stimulation of 5 alpha R activity. Other unlabeled steroid hormones, including progesterone, testosterone, dihydrotestosterone, and estradiol had no significant effect on 5 alpha R activity. (b) In female genital skin fibroblasts, pre-incubation with testosterone also led to an increase in 5 alpha R activity, whereas pre-incubation with estradiol decreased 5 alpha R activity. None of the other unlabeled steroid hormones applied had significant effects. These data on male foreskin in culture suggest a physiologic regulatory mechanism of 5 alpha R activity independent of the concentration of the enzymatic substrate or product, whereas the results for the female genital skin suggest a cellular regulation of the androgen levels by the enzymatic substrate testosterone and a possible negative feedback mechanism of estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Topical imiquimod: a review of its use in genital warts.

UNLABELLED: Imiquimod is a topically active immunomodulatory agent that is formulated as a 5% cream for application by the patient. It is the first agent of its class, the immune response modifiers, to be used in the treatment of genital warts. In immunocompetent patients with genital warts, imiquimod stimulates the production of interferon-alpha and various other cytokines, and has indirect antiviral activity. In randomised, double-blind, vehicle-controlled clinical trials, complete clearance of warts occurred in 37 to 50% of immunocompetent patients with genital warts treated with imiquimod 5% cream 3 times a week for up to 16 weeks; partial clearance of warts (defined as a reduction in wart area of > or = 50%) was observed in 76% of recipients of imiquimod 5% cream. Rates of complete or partial clearance of warts were significantly higher in patients who applied imiquimod 5% cream 3 times a week than in recipients of imiquimod 1% or vehicle cream, each applied 3 times a week. A between-gender difference in clinical response to imiquimod 5% cream has been reported, with female patients experiencing higher rates of complete clearance of warts than males. Recurrence(s) of > or = 1 wart occurred in 13 to 19% of immunocompetent patients in whom complete clearance of warts had been achieved with imiquimod 5% cream. Imiquimod 5% cream also shows some clearance of warts in immunosuppressed HIV-infected patients with genital warts. Preliminary results of a vehicle-controlled study showed that the rate of partial clearance of warts (defined as a reduction in baseline wart area of >50%) [38%] was significantly higher with imiquimod 5% cream than with vehicle cream; however, the rate of complete clearance was not significantly higher than with vehicle cream. Imiquimod 5% cream is generally well tolerated by immunocompetent and HIV-infected patients. Local skin reactions (mainly mild or moderate), including erythema, itching and burning, are the most commonly reported adverse events, occurring in < or = 67% of patients applying imiquimod 5% cream 3 times a week. The incidence of adverse events is lower in patients applying the cream 3 times a week than with daily application. The incidence of systemic adverse events with imiquimod 5% cream (applied daily or 3 times a week) is similar to that of vehicle cream. The tolerability profile of imiquimod cream appears favourable compared with that of podophyllotoxin. CONCLUSION: Imiquimod 5% cream is a new therapeutic option for patients with genital warts. It produces clearance rates broadly similar to those of other treatment approaches and rates of wart recurrence compare favourably with those reported for established treatments. In contrast to most alternative treatment strategies. which are administered in the physician's office, imiquimod cream is a self-administered therapy for outpatient use.

Adjuvants, Immunologic↗
PubMed2006

Famciclovir: a review of its use in herpes zoster and genital and orolabial herpes.

Famciclovir (Famvir) is the oral prodrug of penciclovir, an agent that has demonstrated antiviral activity against herpes simplex viruses, type 1 (HSV-1) and 2 (HSV-2) [which cause orolabial and/or genital herpes simplex], and against varicella zoster virus (VZV) [a reactivation of which leads to herpes zoster]. Famciclovir has efficacy similar to that of aciclovir (in immunocompetent or immunocompromised patients) or valaciclovir (in immunocompetent patients) in the treatment of herpes zoster, and efficacy similar to aciclovir in the treatment of first or recurrent episodes of genital herpes (in immunocompetent or immunocompromised patients). Famciclovir also has efficacy in the suppression of recurrent episodes of genital herpes, and in the treatment of orolabial herpes, in immunocompetent patients. As such, famciclovir is a well tolerated first-line option for the treatment of herpes zoster and the treatment and suppression of genital herpes, and is approved for the treatment of recurrent orolabial herpes. Convenient patient-initiated single-day (for recurrent genital herpes) and single-dose (for orolabial herpes) dosage regimens may contribute to treatment compliance, patient acceptability and subsequent treatment outcomes.

2-Aminopurine↗
PubMed2003

Recurrent genital herpes treatments and their impact on quality of life.

Herpes genitalis is one of the most common viral sexually transmitted diseases in the world, with an estimated seroprevalence in the US of greater than 20%. Two viruses of the same family cause herpes genitalis: herpes simplex virus 1 and 2. After the resolution of primary infection, the virus persists in the nerve roots of the sacral plexus, often causing recurrent (though generally less severe) outbreaks. These outbreaks, as well as the infectious potential to the patient's sexual partners, results in significant psychological stress on the patient, and has a tremendous negative impact on QOL. Current treatment modalities may result in a reduction in the number of outbreaks and viral shedding, but no cure exists. Although studies have clearly demonstrated the negative impact of recurrent genital herpes on QOL, an assessment scale specific to herpes was not developed until recently. Earlier studies indicated that patients did not perceive a significant benefit from episodic treatment with antivirals, but studies using the Recurrent Genital Herpes Quality of Life Questionnaire (RGHQoL) have now demonstrated that suppressive antiviral therapy improves quality of life in patients with frequent recurrences of genital herpes. However, not all patients with recurrent genital herpes need suppressive therapy, and proposed factors to consider include frequency of recurrence, physical and psychological distress caused by recurrences, and the potential for transmission to the patient's sexual partner. Newer therapeutic modalities, including the topical immune response modifier resiquimod and herpes vaccines, may eventually be shown to further decrease the psychological morbidity of recurrent genital herpes.

2-Aminopurine↗
PubMed2005

Psychological symptoms associated with genital herpes virus infections: epidemiology and approaches to management.

Genital herpes is a common, chronic, recurrent, viral sexually transmitted infection (STI) occurring worldwide. The first episode may be severe and prolonged, but most recurrences are usually short lived and minor. Although most individuals with this infection have no symptoms, STIs, including genital herpes, often cause psychological and psychosexual morbidity. Unfortunately, the existing data on the psychological symptoms associated with genital herpes have many limitations, including anecdotal reporting, evaluation of small and selected populations, use of varied and sometimes unevaluated questionnaires, and lack of controls. Some individuals with recurrent genital herpes display a range of emotional responses, including depression, anguish, distress, anger, diminution of self-esteem and hostility towards the person believed to be the source of infection. However, it is always important to consider the possibility of pre-existing psychopathology. Several retrospective studies have suggested that stress could lead to recurrences of genital herpes infection. However, prospective studies have been unable to demonstrate any relationship between pre-existing stress and recurrences. What these studies were able to demonstrate was that stress and recurrences occurred simultaneously, suggesting that perhaps it was the recurrences that were causing stress, rather than the reverse.

Disease Management↗
PubMed2006

Importance of herpes simplex virus type-1 (HSV-1) in primary genital herpes.

Herpes simplex virus type 1 (HSV-1) is increasingly reported in primary genital herpes. Its incidence was assessed among Rotterdam sexually transmitted diseases clinic attendees between 1996 and 2001, and demographic and sexual behaviour factors were evaluated. A retrospective record analysis was performed. All herpes diagnoses were based on cell culture techniques. A clinical scoring system was used to select "primary" cases. Demographic and sexual behaviour characteristics were analysed using logistic regression. The clinical scoring system showed 115 cases of primary genital herpes. HSV-1 (n = 60) was found in 52% and HSV-2 (n = 55) in 48% of cases. The multiple logistic regression model showed that HSV-1 was associated with "oro-genital contact" (p < 0.001) and "having a single partner in the last 2 months" (p = 0.054) and that HSV-2 was associated with "a higher number of sexual partners in the last 6 months" (p = 0.085). Our data confirm the growing importance of HSV-1 in primary genital herpes; oro-genital sex is the main risk factor.

Adolescent↗
PubMed2006

Unexpectedly high frequency of genital involvement in women with clinical and histological features of oral lichen planus.

The main aims of this cross-sectional study were: (i) to assess the frequency of genital (vulval) lichen planus (VLP) and vulval lichen sclerosus (VLS) in women affected with oral lichen planus (OLP), regardless of the genital symptoms reported; and (ii) to verify whether any demographic, clinical, or histological features of OLP are associated with a higher risk of vulvo-vaginal involvement. Fifty-five women, presenting OLP, consecutively underwent gynaecological examination and, if they demonstrated positive clinical signs of VLP, underwent biopsy. After a drop-out of 14 subjects, 31/41 (75.6%) were found to have signs of genital involvement, of which 13/31 (44.0%) were asymptomatic. Following genital biopsy, 27/31 (87.1%) had histologically confirmed VLP or VLS. Following both univariate and multivariate statistical analyses, no significant association was found between gynaecological concomitance and demographic, clinical, histological features of OLP. This unpredictably common genital involvement in females with OLP emphasizes the importance of routinely performing both oral and gynaecological examinations, to facilitate an early and correct therapeutic approach.

Adult↗
PubMed2006

Genital ulcers as initial manifestation of Epstein-Barr virus infection: two new cases and a review of the literature.

Genital ulceration is an uncommon manifestation of primary Epstein-Barr virus (EBV) infection. We present here two cases of genital ulcers probably caused by EBV. The first case is a 12-year-old girl with a genital ulcer appearing before specific EBV serology could identify a primary infection. However, serology was positive 13 days after the ulcer appeared. Polymerase chain reaction for EBV was positive in the biopsy from the ulcer as well. The second case is an 18-year-old female in whom the specific EBV serology was positive 8 days after appearance of the ulcer. The ulcers in both cases healed after 21 days. We reviewed the literature and a total of 26 cases of EBV-associated genital ulcers in females are now published. Median age of the 26 cases is 14.5 years of whom only 6 reports previous sexual contact. Mean healing time for the ulcers is 18 days. Our two cases correspond well with clinical reports of 24 EBV-associated genital ulcers in the literature.

Adolescent↗
PubMed1989

Counseling clients with genital herpes.

The epidemic of genital herpes requires nurses to diagnose and treat human responses to this health problem (American Nurses' Association, 1980). It also creates many opportunities for nurses, particularly in the realm of counseling and education. Given the changing epidemiology of genital herpes and the psychosocial consequences, nurses need to keep abreast of new information so that they may assist people to live with the disease and teach the prevention of transmission of the disease. Recent information about mild and asymptomatic cases of herpes infections has serious implications for counseling and education of persons with genital herpes. The emergence of this "silent" dimension of herpes infections means more difficulty in diagnosis and treatment. All persons with genital herpes should be assessed for their physical and psychological responses to the disease and information should be given to combat misconceptions, to alleviate fear, and aid in preventing transmission. The most significant implication of mild or asymptomatic herpes is the greater risk of transmission. The public needs to be informed about the practice of "safer sex" as a routine measure to prevent herpes, as well as AIDS and other STDs. Given the widespread and epidemic proportions of herpes, persons should be counseled to use condoms whenever they engage in sexual activity with a partner. In addition, correct use of condoms must be taught. Nurses have an important role to play in counseling clients with genital herpes and in preventing the disease.

Adaptation, Psychological↗
PubMed2005

Neurokinin 1 receptor signaling affects the local innate immune defense against genital herpes virus infection.

We show that genital infection with neurotropic HSV type 2 (HSV-2) induced a significant increase of the neuropeptide substance P (SP) within the genital tract of mice. SP was shown to weakly interfere with the HSV-2 replication. Furthermore, lack of SP signaling through the use of mice deficient in the SP receptor, neurokinin 1 receptor (NK1R), revealed an important role for SP in the innate defense against HSV-2. NK1R-deficient mice had significantly enhanced levels of HSV-2 in the genital tract and in the CNS following infection and a significantly accelerated disease progression, which was associated with an impaired NK cell activity locally in the vagina. Lack of NK1R signaling did, however, not impair the animals' ability to mount a protective immune response to HSV-2 following vaccination with an attenuated virus. Both NK1R+/+ and NK1R-/- mice developed strong HSV-2-specific Th1 T cell responses following vaccination. No genital viral replication was observed in either vaccinated NK1R-deficient or NK1R+/+ control animals following a genital HSV-2 challenge, and all of these animals survived without any symptoms of disease. In conclusion, the present results indicate that SP and NK1R signaling contributes to the innate resistance against HSV-2 infection in mice.

Animals↗
PubMed1992

Risk factors for the sexual transmission of genital herpes.

OBJECTIVE: To determine the risk of sexual transmission of genital herpes simplex virus (HSV) in heterosexual couples. DESIGN: Prospective study of couples who were participants in a clinical trial. Each source partner had symptomatic, recurrent genital HSV, and each susceptible partner was without serologic or clinical evidence of genital herpes. Couples were followed for a median of 334 days. SETTING: Two university-based research clinics. PATIENTS: One hundred forty-four heterosexual couples were studied out of an initial enrollment of 214 couples. MAIN OUTCOME MEASURES: Development of culture-proven HSV infection or type-specific antibodies in the susceptible partner. MAIN RESULTS: Transmission occurred in 14 (9.7%) couples, including 11 (16.9%) of 65 couples with male and 3 (3.8%) of 79 with female source partners (P = 0.05). The annual rate of acquisition was higher (31.8%) in susceptible female partners who lacked antibodies to either HSV type 1 or 2 at entry compared with females with HSV type 1 antibodies at entry (9.1%). Couples avoiding transmission of HSV reported fewer days with genital lesions in source partners. Detailed histories were available at the time of transmission in 13 couples. In nine couples, transmission occurred when the source partner was reported to be asymptomatic and in four, it resulted from sexual contact at the time of prodrome (1 case) or within hours before lesions were first noticed by the source partner (3 cases). CONCLUSIONS: Despite clear recognition of genital herpes in source partners, there was substantial risk for transmission; in 70% of patients, transmission appeared to result from sexual contact during periods of asymptomatic viral shedding. The risk for acquisition of HSV was higher in women than men, and previous HSV type 1 infection appeared to reduce the risk for acquisition of HSV type 2 infection among women.

Adult↗
PubMed1982

The epidemiology of genital colonization with Staphylococcus aureus.

The prevalence of genital colonization with Staphylococcus aureus, including strains that have been associated with toxic shock syndrome, was studied in 600 women. Nine percent of these women were colonized with S. aureus, 5% of whom had positive vaginal cultures, and 1% were colonized with toxin-producing strains. Black women were colonized with S. aureus, including toxin-producing strains, as frequently or more frequently than white women. The highest colonization rates occurred in postpartum women. Trends toward increasing colonization occurred in relation to decreasing age and socioeconomic status. There were no statistically significant relationships between genital colonization with S. aureus and the use of tampons, oral contraceptives, or a variety of other personal habits and health problems. Genital cultures taken in consecutive menstrual cycles indicated that 35% of women with S. aureus were persistent carriers, and the rest either intermittent or transient carriers. Toxin-producing S. aureus was also identified in family members of women carrying the same organism. This report defines the prevalence of genital colonization in a large population of women, characterizes the women with S. aureus, and describes epidemiologic features of genital carriage.

Adolescent↗
PubMed1999

[Importance of defecography in the evaluation of genital prolapses].

OBJECTIVE: To determine the interest of defecography for the initial evaluation of genital prolapses. PATIENTS AND METHODS: A retrospective study of 125 patients who had undergone systematically a defecography for the initial evaluation of a genital prolapse. RESULTS: 10% of defecogaphies were normal. On clinical examination a rectocele was found in 94% of patients and an enterocele in 33%. At defecography, these abnormalities were seen only in 39% and 15% respectively. 39% of patients with radiological rectocele had an intussusception at defecography. CONCLUSION: Defecography is appropriate to diagnose and to assess constitutional abnormalities associated with genital prolapse (rectocele, enterocele) and other anomalies which interact with it (intussusception, sphincter and pubo-rectal dyskinesia). Most of women with genital prolapse showed abnormal defecograms. We observed a marked discordance between clinical and radiological evaluation, specially for rectocele. Defecography is of great interest in the evaluation of posterior genital prolapses, specially in women complaining of dyschesia. Defecography may be proposed in case of: posterior vaginal wall prolapse (rectocele, enterocele), dyschesia, post-operative prolapse and before a cervicopexy.

Defecography↗
PubMed1999

[Disorders of pulmonary ventilation function in patients with genital prolapse in postmenopause].

Low collagen contents in urogenital organs and skin were found in women with genital descensus, pointing to genetic abnormalities in connective tissue as the underlying cause. Since lungs have abundant connective tissue and depend on its integrity we hypothesized that postmenopausal women with genital descensus may have pulmonary function disorders. Therefore, in the sample of 66 inpatients that were planned for surgical correction of genital descensus, the pulmonary ventilatory function was evaluated and compared to 67 matched volunteers without genital descensus. All examinees were in postmenopausis, nonsmokers and without history or clinical signs of the diseases that are known to affect the pulmonary function. All subjects were interviewed, gynecologically examined and performed the dynamic spirometry (MASTERLAB, Jaeger). Statistically significant reductions in vital capacity and forced expiratory volume at 1st second were observed. However, the initial expiratory flows were greatly reduced, mostly the peak expiratory flow (for 40%) and the forced expiratory flow at 75% and 50% of forced vital capacity (for 39% and 35%). These findings are consistent with reduced strength of expiratory muscles and point towards possible association of the lack of collagen and the impairment in pulmonary function in postmenopausal women with genital descensus.

Collagen Diseases↗
PubMed2000

Recent advances in management of genital herpes.

OBJECTIVE: To provide an update on new diagnostic tests and antiviral strategies for managing genital herpes. QUALITY OF EVIDENCE: Treatment guidelines are based on randomized clinical trials and recommendations from the Expert Working Group on Canadian Guidelines for Sexually Transmitted Diseases. Recommendations concerning other aspects of managing genital herpes (e.g., indications for using type-specific serologic tests) are mainly based on expert opinion. MAIN MESSAGE: Genital herpes is one of the most common sexually transmitted diseases, affecting about 20% of sexually active people; up to 80% of cases are undiagnosed. Because of frequent atypical presentation and the emotional burden associated with genital herpes, clinical diagnosis should be confirmed by viral culture. Type-specific serologic assays are now available, but their use is often restricted to special situations and requires adequate counseling. New antivirals (valacyclovir and famciclovir) with improved pharmacokinetic profiles have now been approved for episodic treatment of recurrences and suppressive therapy. CONCLUSION: Wise use of new diagnostic assays for herpes simplex coupled with more convenient treatment regimens should provide better management of patients with genital herpes.

2-Aminopurine↗
PubMed2001

Use of type-specific HSV serology in the management of a 37-year-old woman diagnosed with primary genital herpes.

A 37-year-old woman attended a Genitourinary Medicine Clinic in London, UK, concerned about the reliability of a culture-based diagnosis of genital herpes that she had received while abroad. She was in a longterm monogamous relationship with a partner who recalled no history of genital herpes. She was unsure as to how she had acquired genital herpes and wished to know whether she was newly infected. Typespecific serological testing indicated a true primary herpes simplextype-2 (HSV-2) infection. The patient's partner did not attend the clinic but reported a (negative blood test for herpes) at a clinic elsewhere. No details were provided as to the type of assay used, so the possibility that this result was inaccurate cannot be ruled out. It is possible that he may have been an asymptomatic carrier of HSV (either HSV-2 or both HSV-1 and-2) or had mild unrecognized symptoms of genital HSV. This case highlights the advantages and pitfalls of using a type-specific serological test for the diagnosis of genital herpes and also the need for appropriate counselling. An initial explanation of the significance of the HSV culture result she received abroad may have reduced the patient's anxiety about the reliability of the initial diagnosis.

Adult↗
PubMed2002

The clinical management of recurrent genital herpes: current issues and future prospects.

This article reports the proceedings of an expert panel discussion on current clinical management practices for the treatment of recurrent genital herpes. The panel reviewed the effectiveness of primary and specialist care settings in the UK and USA and identified the principal clinical needs of patients with recurrent genital herpes. The ideal alternative to daily suppressive nucleoside analogue therapy is a treatment with long-term impact on the natural history and prognosis of recurrent genital herpes. The potential of resiquimod, an immune response modifier, to resolve this unmet need was examined. Resiquimod is reported to delay the onset of recurrent genital herpes symptoms in patients in a Phase II clinical trial. While awaiting clinical confirmation of this new development in immunotherapy, the panel concluded with two recommendations: a reassessment of recurrent genital herpes management in terms of physician education of patients, and the promotion of a positive patient-physician relationship in the approach to treatment.

Adjuvants, Immunologic↗