Sulpiride infused into the nucleus accumbens posttraining impairs memory of spatial water maze training

A randomized, double-blind study of valaciclovir for suppression of recurrent genital herpes was conducted among 1479 immunocompetent patients. Patients were randomized to receive valaciclovir (250 mg, 500 mg, or 1 g once daily, or 250 mg twice daily), acyclovir (400 mg twice daily), or placebo, for 1 year. All valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences (P < .0001). There was a dose-response relationship (P < .0001) across the once-daily valaciclovir regimens. Twice-daily valaciclovir and acyclovir were similar in effectiveness. Subgroup analysis showed that patients with a history of < 10 recurrences per year were effectively managed with 500 mg of valaciclovir once daily. One gram of valaciclovir once daily, 250 mg of valaciclovir twice daily, or 400 mg of acyclovir twice daily were more effective in patients with > or = 10 recurrences per year. Safety profiles of all treatments were comparable. Thus, valaciclovir is highly effective and well tolerated for suppression of recurrent genital herpes. Once-daily regimens offer a useful option for patients who require suppressive therapy for management of genital herpes.     

Peroral famciclovir in the treatment of experimental ultraviolet radiation-induced herpes simplex labialis: A double-blind, dose-ranging, placebo-controlled, multicenter trial

Three doses of famciclovir were tested for treatment of experimental ultraviolet radiation (UVR)-induced herpes labialis. Patients received 125, 250, or 500 mg of famciclovir or placebo 3 times a day for 5 days beginning 48 h after UVR exposure, a model of early episodic intervention. Of 248 patients irradiated, 102 developed lesions while on treatment. There were no significant differences between groups in the number of lesions. The mean maximal lesion size was reduced in a dose-proportional manner: 139, 105, 77, and 55 mm2 for the placebo and 125-, 250-, and 500-mg famciclovir groups, respectively (P=.040, linear regression). Median time to healing was faster in the 500-mg famciclovir group than in the placebo group, both by investigator (4 vs. 6 days, 33% reduction, P=.010) and patient assessment (3.0 vs. 5.8 days, 48% reduction, P=.008) analyses. These findings suggest that evaluation of higher drug doses for herpes labialis treatment is warranted.     

Evidence of latency and reactivation of both herpes simplex virus (HSV)-1 and HSV-2 in the genital region

While superinfection with different herpes simplex virus (HSV) types has been demonstrated in animals, the ability of the two HSV types to colonize and reactivate in the same anatomic region in humans has not been well demonstrated. In 6 patients, both HSV-1 and HSV-2 was recovered from genital lesions. In 4 of them, who initially acquired genital HSV-1 infection, subsequent HSV-2 infection presented as a prolonged episode of genital lesions and a marked increase in the frequency of genital recurrences. While most of the subsequent clinical reactivations were HSV-2, in 2 patients the recurrence rate of genital HSV-1 increased after the acquisition of HSV-2. These data demonstrate the ability of a second HSV type to infect the same anatomic region and illustrate the difference in reactivation frequency of the two types in the same person. Typing of HSV isolates may be useful in persons with recent alteration in recurrence rates of genital HSV.     

Detection of viral DNA to evaluate outcome of antiviral treatment of patients with recurrent genital herpes

Culture of infectious virus, PCR amplification of viral DNA, and the appearance of genital skin lesions were used as markers to study the course of a recurrence of genital herpes in 40 patients treated with famciclovir or placebo. The highest frequency of patients with skin lesions occurred within the first 36 h following the onset of a recurrence, which also corresponded to the peak in the production of virus. While the timing of the peak in skin lesions was independent of the type of treatment, the frequency of lesions and the release of virus at the lesion site were both reduced by famciclovir treatment. Furthermore, patients receiving this antiviral agent showed a more rapid recovery time and a shorter period during which viral DNA could be detected at the lesion. PCR and then Southern blot hybridization greatly enhanced our ability to detect herpes simplex virus at the lesion site. This procedure proved to be of greater diagnostic value in assessing genital herpes than the standard culture method currently used. In addition, PCR was more sensitive in evaluating treatment effectiveness.     

Herpes. Atypical clinical manifestations

Herpes simplex viruses (HSV) 1 and 2 are responsible for genital herpes which is usually recognized as vesicles that ulcerate and eventually heal but recur periodically. Atypical genital herpes is often described in immunocompromised patients and can present as large, chronic, hyperkeratotic ulcers. Acyclovir-resistant HSV is occasionally isolated from such ulcers. Most cases of HSV infection reproduce subtle signs and symptoms, or more commonly, asymptomatic viral shedding. Such subclinical presentations may be responsible for most of the 30% increase in the prevalence of genital herpes in the United States during the past two decades.     

Human leukocyte interferon-alpha in a hydrophilic cream versus in a gel for the treatment of genital herpes in males: a placebo-controlled, double-blind, comparative study

The aim of this double-blind, placebo-controlled, comparative study was to differentiate the clinical efficacy and tolerability of human leukocyte interferon-alpha incorporated (2 x 10(6) IU/g) in a hydrophilic cream and in a gel to heal males afflicted with first episodes of genital herpes. Patients (n = 60), aged 18-40 years (mean 23.2) with culture-confirmed diagnosis of herpes genitalis were randomized to three parallel groups. Each patient was allocated a precoded 40-g tube, containing either preparation or placebo. Cream or gel was applied three times daily for 5 consecutive days. The duration of the active treatment was two weeks. Patients were examined after 48 hours in initial treatment, and thereafter two times a week. A reepithelialized lesion with some residual erythema was recorded as healed. The study demonstrated that patients treated with leukocyte interferon-alpha cream had both significantly shorter mean duration of lesions than gel and placebo recipients (5.3 days vs. 8 days, 13 days respectively; p < 0.001) and a higher number of healed patients (80% vs. 55%, 20% respectively; p < 0.001). Of the 60 patients, 49 (82%) complained of no drug-related side effects. Eleven patients predominantly in the cream/gel groups reported non-objective transitory increase in their body temperature (> 38 degrees C) with moderate headache, malaise and myalgia. The study was followed-up for 24 months after the first day of the treatment, and out of 31/60 cured patients, 4 had a relapse after 18 months. In conclusion the study affirmed that human leukocyte interferon-alpha (2 x 10(6) IU/g) in a hydrophilic cream is more efficacious than its incorporation in gel or placebo, thus suggesting that leukocyte interferon-alpha in a hydrophilic cream, with a profile of non-objective mild to moderate drug-induced indications, may be considered an alternative and effective treatment modality to cure male patients afflicted with first episodes of genital herpes.     

Immunotherapy of recurrent genital herpes with recombinant herpes simplex virus type 2 glycoproteins D and B: results of a placebo-controlled vaccine trial

To determine the safety, immunogenicity, and efficacy of a recombinant herpes simplex virus type 2 glycoprotein D and B vaccine in the treatment of recurrent genital herpes, a randomized, placebo-controlled trial was held at two referral centers. Healthy patients with 4-14 recurrences per year received injections of both glycoproteins in MF59 adjuvant or of MF59 alone at 0, 2, 12, and 14 months. For 18 study months, the rate and number of recurrences, the duration and severity of the first confirmed recurrence, vaccine immunogenicity, and rates of local and systemic reactions were determined. The monthly rate of recurrences was not significantly improved, but the duration and severity of the first study outbreak was reduced significantly by vaccination. Glycoprotein-specific and neutralizing antibodies were boosted by vaccination for the duration of the study. This vaccine is safe and immunogenic and ameliorated an observed first postvaccination genital recurrence, but it does not reduce recurrence frequency.     

DNA immunization against experimental genital herpes simplex virus infection

A nucleic acid vaccine, expressing the gene encoding herpes simplex virus (HSV) type 2 glycoprotein D (gD2) under control of the cytomegalovirus immediate-early gene promoter, was used to immunize guinea pigs against genital HSV-2 infection. The vaccine elicited humoral immune responses comparable to those seen after HSV-2 infection. Immunized animals exhibited protection from primary genital HSV-2 disease with little or no development of vesicular skin lesions and significantly reduced HSV-2 replication in the genital tract. After recovery from primary infection, immunized guinea pigs experienced significantly fewer recurrences and had significantly less HSV-2 genomic DNA detected in the sacral dorsal root ganglia compared with control animals. Thus, immunization reduced the burden of latent infection resulting from intravaginal HSV-2 challenge, and a nucleic acid vaccine expressing the HSV-2 gD2 antigen protected guinea pigs against genital herpes, limiting primary infection and reducing the magnitude of latent infection and the frequency of recurrent disease.     

Prevalence of herpes simplex virus type 1- and 2- specific antibodies among the acute, recurrent, and provoked types of female genital herpes

Sixty-eight sera from the acute, recurrent, and provoked types of female genital herpes were compared for the seroprevalence of herpes simplex virus (HSV) types 1 and 2 by immunodot assay using HSV glycoprotein G. In the HSV-1-isolated patients, no HSV-2 antibodies were detected, whereas in the HSV-2-isolated patients, HSV-1 seroprevalence was 9% for the acute type, 89% for the provoked type (P < 0.005), and 55% for the recurrent type (P < 0.05). The natural history of female genital herpes and the possible protective role of pre-existing antibodies in preventing the acquisition or clinical manifestation of a subsequent HSV infection are discussed.     

The relationship among genital herpes simplex virus, stress, and social support.

Examined the role of stress in activation of genital herpes simplex virus (HSV) lesions, as mediated by social support, in 59 adults who had self-reported culture-positive genital HSV for at least 10 mo. Retrospective reports of HSV symptoms revealed that duration of disease and herpes-specific social support were significant moderators of the relation between stress and number of HSV recurrences (HSV-R) in the preceding 12 mo. When duration of disease was short (     

Genital herpes: epidemiology and pathophysiology. Update and new perspectives

Genital Herpes simplex virus (HSV) is a sexually transmitted disease (STD) which affects millions of people worldwide and is mainly due to HSV type 2. Seroprevalence rates as high as 60-90% have been reported in developing countries. In developed countries, 20% of the general population is HSV2 seropositive. Recent epidemiological surveys employing type-specific antibody assays show that the prevalence of HSV-2 infections is rising at an alarming rate. Also, the epidemiology is changing with an increasing incidence of first episodes caused by HSV-1. The natural history of HSV infection includes acute or subclinical first episode mucocutaneous infection, establishment of neuronal latency, and intermittent virus reactivation with or without associated symptoms. Although this sequence of events has been recognized for more than five decades, little is known about the exact mechanism of latency and reactivation. Almost all persons with HSV2 infection will have recurrences. Recent data show that many of these infections are subclinical: subclinical shedding can be documented in over 80% of HSV2 seropositive individuals who deny subclinical lesions. This suggests that patients shed virus and transmit it even in the absence of clinical signs and that genital herpes should be redefined as a chronic rather than an intermittent disease.     

Psychological investigation of genital herpes recurrence: Prospective assessment of cognitive-behavioral intervention for a chronic physical disorder.

Assessed factors associated with genital herpes and investigated the impact of psychological therapy on 16 patients who received 5 wks of structured discussion or cognitive restructuring (CR) group therapy. Measures of attitude about herpes, global coping, distress, loneliness, health locus of control, and recurrence were administered at pre- and posttreatment and at 3 mo follow-up. Information was extracted from daily self-reports regarding herpes symptoms, dysphoria, anxiety, and ongoing coping. Therapy did not produce expected reductions in distress or loneliness. CR, however, was associated with reduced frequency of lesion recurrence at follow-up. Avoidant coping was associated with lower recurrence rates, and loneliness scores with higher rates. Results show that recurrences were preceded by elevated anxiety independent of prodromal symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Frequent use of menfegol spermicidal vaginal foaming tablets associated with a high incidence of genital lesions

Menfegol is a spermicide with in vitro activity against human immunodeficiency virus (HIV). A randomized placebo-controlled safety study covered the use of menfegol foaming tablets for 14 days at increasing frequencies of insertion by 125 prostitutes in Dakar, Senegal. The frequencies of colposcopically diagnosed genital lesions were 5.0%, 11.8%, 27.8%, 49.7%, and 29.4% among menfegol recipients when tablets were used once every other day or 1, 2, 4, or 8 times a day, respectively (P < .05). Among placebo recipients, frequencies were 11.1% and 23.5% when tablets were used < 8 times daily and 8 times daily, respectively. There was no association between subjective genital symptoms and the incidence of colposcopically detected lesions. The high incidence of genital lesions when menfegol foaming tablets were used more than once daily suggests that their frequent use should not be recommended to prevent HIV transmission. In use at low frequency, the tablets' toxicity might be balanced by anti-HIV properties. Safety studies on vaginal microbicides should use objective methods, such as colposcopy, to assess the incidence of lesions.     

Advances in the treatment of herpesvirus infection: the role of famciclovir

Shingles (herpes zoster) is the result of reactivation of varicella-zoster virus after years of latency. The acute phase is self-limiting but is often associated with moderate-to-severe pain; postherpetic neuralgia is the most frequent and debilitating complication of shingles, occurring in 3.4 per 1000 individuals per year. In the case of genital herpes, herpes simplex virus can reactivate to cause recurrent episodes as often as several times a year, sometimes for the remainder of a person's life. Antiviral agents such as famciclovir, valacyclovir, and acyclovir can be used to shorten the course and decrease the severity of these diseases and may suppress the virus itself, thereby preventing future outbreaks of genital herpes. This article presents a brief synopsis of the etiology of herpes zoster and genital herpes and reviews 12 key studies that demonstrate the efficacy of famciclovir in the management of these two conditions.     

Genital herpes infection: a review

Genital herpes infection is life-long and may result in painful and recurrent genital lesions, systemic complications, serious psychosocial morbidity, and rare but serious outcomes in neonates born to infected women, including permanent neurological handicap and death. Herpes simplex virus (HSV)-2 is the principal cause, with an increasing proportion of first-episode disease caused by HSV-1. Genital HSV transmission is usually due to asymptomatic viral shedding by people who are unaware that they are infected and clinical screening fails to detect most infections. Type-specific serological assays can distinguish the two viral subtypes, but these are expensive and currently restricted to a few research settings. Most infections are asymptomatic, or cause a mild illness which does not lead to health service attendance; but the limited evidence suggests a rise in disease incidence, perhaps related to a fall in HSV-1 age-specific prevalences. The prevalences of HSV genital infections increase with age and numbers of sexual partners, with higher rates in specific ethnic and low socioeconomic groups. However, infection is not restricted to high-risk populations. Antiviral agents, such as acyclovir, can reduce disease severity, prevent recurrences and shorten periods of viral shedding, but currently there are no effective population control measures. This may change with the advent of HSV vaccines, if their safety and long-term efficacy are confirmed. Possible applications for vaccines may include the suppression of disease and recurrences in patients with genital infections (immunotherapy), the prevention of viral transmission to their seronegative partners, and immunoprevention through vaccinating the latter. Economic evaluations of existing and potential control strategies, age-specific population HSV-1 and 2 seroprevalence studies for targeting future interventions, and cohort studies to elucidate the natural history of HSV-2 infections are needed.     

Protective vaccination against primary and recurrent disease caused by herpes simplex virus (HSV) type 2 using a genetically disabled HSV-1

The vaccine potential of a mutant herpes simplex virus (HSV) type 1, with a deletion in the glycoprotein H (gH) gene, was evaluated. The virus requires a gH-expressing cell line for multi-cycle growth but can complete a single cycle of infection in noncomplementing cells. Such viruses, termed DISC (disabled infectious single cycle) viruses, should be safe, yet still able to stimulate humoral and cell-mediated responses against a broad range of virus antigens in vaccinated hosts. Prophylactic vaccination of guinea pigs with DISC HSV-1, by ear scarification or direct infection of the vaginal mucosa, afforded a high degree of protection against HSV-2-induced primary genital disease and reduced significantly the frequency of subsequent disease recurrence. There was also a trend toward reduced recurrence following therapeutic vaccination of animals already infected with HSV-2. DISC HSV vaccination, therefore, offers an effective route for control of HSV disease.     

Recurrent Mollaret's meningitis of herpetic origin

BACKGROUND: Benign recurrent meningitis, or Mollaret's meningitis, is an uncommon disease whose viral origin was long unidentified. Since 1991, about twenty cases have been reported in patients with herpes infection. CASE REPORT: A female patient had experienced repeated episodes of spontaneous meningitis since 1983. The episodes resolved spontaneously and no etiology had been identified. A spinal tap was performed when the patient was again hospitalized a new episode of meningitis and PCR amplification of the herpes simplex virus type 2 (HSV 2) was positive. The patient was given long term acyclovir per os. A new spinal tap after resolution of the meningitis episode was PCR HSV2 negative. DISCUSSION: HSV2 infection is one of the known causes of Mollaret's meningitis. Long-term antiviral therapy appears to prevent recurrence as was observed in our patient.     

Diet diversity and gastric cancer

PURPOSE: To document a case of acute retinal necrosis syndrome in an immunocompetent patient who was successfully treated with famciclovir after unsuccessful treatment with acyclovir. METHODS: After diagnosing acute retinal necrosis syndrome in the patient's left eye, we treated him with 13 mg/kg/24 hours of intravenous acyclovir in three daily doses for 14 days, followed by 800 mg of acyclovir five times per day orally. New areas of retinitis developed within the posterior pole despite treatment with the maximum dosage of acyclovir; thus, we used a new antiviral agent, famciclovir. RESULTS: When we administered 500 mg of famciclovir orally every 8 hours for 3 months, the retinitis regressed within 1 month, leaving atrophic granular pigmented scars. CONCLUSION: Famciclovir can effectively treat acute retinal necrosis syndrome in immunocompetent patients.     

A randomized double-blind trial comparing cibenzoline and disopyramide in the prevention of recurrences of atrial tachyarrhythmia

The aim of this multicenter, randomised, double-blind trial was to compare the efficacy and tolerance of oral disopyramide (D: 250 mg slow release twice daily) compared with cibenzoline (C: 130 mg twice daily) in the prevention of recurrences of atrial arrhythmias over a 6 month period. Sixty patients (mean age: 62 +/- 14 years; 37 men, 23 women; cardiac disease in 60% of cases) were randomised to two groups: C (N = 31) and D (N = 29). The commonest arrhythmia was atrial fibrillation (83%). The arrhythmia was recent (< 3 months) in 41% of patients and present for more than one year in 38% of patients. Sixteen patients of Group C (52%) and 11 of Group D (38%) had recurrences after an average of 79 +/- 58 days for Group C and 58 +/- 40 days for Group D (p = NS). The probability of absence of recurrence at 6 months was 36 +/- 11% in Group C and 55 +/- 10% in Group D (p = NS). Four patients in Group C (13%) and 13 patients in Group D (45%) had at least one unwanted side-effect (p = 0.009). Treatment was stopped because of side-effects in 2 patients in group C (6%) and 6 patients in Group D (21%). These results show that cibenzoline has a comparable efficacy for the prevention of recurrence of atrial tachyarrhythmia and is significantly better tolerated than disopyramide. This differences is mainly related to the marked anticholinergic effects of disopyramide.     

Comparative sequence of human and mouse BAC clones from the mnd2 region of chromosome 2p13

The antiviral effect of acyclovir elaidate in the female guinea pig model of genital herpes was investigated in a series of experiments. The antiherpesvirus effects of this novel compound, 9-(2'-[trans-9"-octadecenoyloxyl]ethoxymethyl)guanine (code no. P-4010), were studied in both primary and recurrent genital herpes in the female guinea pig, following oral gavage or intraperitoneal injection, with different formulations of the compound, and in comparison with acyclovir (ACV) or penciclovir (PCV). The results indicate that compound P-4010 has a greater capability than either ACV or PCV in reducing the clinical symptoms of primary genital herpes induced following the inoculation of herpes simplex virus type 2 (HSV-2) intravaginally into guinea pigs. In addition, the administration of P-4010 twice daily over a 10-day period by the intraperitoneal route (15 to 40 mg/kg of body weight/day) or by oral gavage (50 to 200 mg/kg/day), commencing 4 h subsequent to intravaginal HSV-2 infection, resulted in a degree of reduction in the incidence and severity of spontaneous, recurrent genital herpes in these animals. The findings are discussed in the light of the value and relevance of the female guinea pig model of genital herpes for the assessment of anti-herpes simplex virus compounds.