Early syphilis in a man with a negative Treponema pallidum enzyme immunoassay-IgM.

Most serological tests for syphilis rely on an individual's ability to produce antibodies. A single screening test may be unreliable for screening in those with primary immunodeficiency. We present the first reported case of primary and secondary syphilis with negative Treponema pallidum enzyme immunoassay-IgM and Venereal Disease Research Laboratory tests in a man with common variable immunodeficiency.

Chlamydia screening programme, HMP Hydebank Wood Young Offender Centre, Belfast, Northern Ireland, UK.

In a young offender's centre, 204 male prisoners were offered chlamydia screening, from January 2007 to April 2007. The aim of this screening programme was to identify and treat asymptomatic prisoners with chlamydia infection. Offering the screening within a prison was an opportunity to test a hard-to-reach population that is at high risk of chlamydia infection. The programme established a high level of testing acceptability with a 98% screening uptake rate. Using nucleic acid amplification testing, 21 (10.5%) tested prisoners were positive for Chlamydia trachomatis. Patients were treated under Patient Group Direction (PGD). Further screening for sexually transmitted diseases was offered to chlamydia-positive patients by the genitourinary (GU) medicine specialist.

How does HIV impact on non-AIDS events in the era of HAART?

Death rates from AIDS-related events in HIV-positive individuals have declined in the era of highly active antiretroviral therapy (HAART). It has also been shown that deaths from non-AIDS events have declined in this cohort since the advent of HAART. We review these data, as well as discussing some of the possible effects HAART might have on non-AIDS diagnoses and deaths in HIV-positive individuals with successfully treated HIV.

What you can see in your patient's eyes? Review of ocular manifestations of HIV in HAART era.

The early diagnosis and treatment of ocular disease to prevent morbidity and mortality of patients with human immunodeficiency virus (HIV) is of paramount importance. Since the advent of highly active antiretroviral therapy (HAART), the incidence of ocular complications of HIV has decreased and their manifestations and natural course are also modified. This has been observed in the face of emerging immune recovery, which per se has brought new difficulties in the process of diagnosing and management of the ocular disease. Conditions such as immune recovery uveitis could affect eyes with history of opportunistic disease with a potential to cause vision loss; with this regard, differentiation of the inflammatory process from infective causes is essential. The other sexually contracted diseases are also to be included in this complex picture because of their contribution to the clinical picture and also sharing common routes of transmission with HIV. There is very little doubt that visual deterioration would further deteriorate the already compromised quality of life of this group of patients. In this review, authors wish to provide evidence available in the medical literature around the visual health issues in HIV-infected patients and raise awareness towards the changing pattern of the ocular disease in the HAART era.

Genital schistosomiasis.

Schistosomiasis is the most serious helminthic infection in the United Kingdom. Female genital schistosomiasis affects 9-13 million women worldwide, mainly in areas where Schistosoma haematobium is endemic. With increasing tourism to these areas, this diagnosis is being encountered more frequently in the West. We present 2 cases of vulval schistosomiasis that were presented to our department in 1999 and 2000.

The ultrasound investigation of scrotal swelling.

The objectives of this study were to: (1) establish the causes of scrotal swelling in the hospital catchment population; (2) define the role of high frequency ultrasound examination in the management of scrotal swelling. A retrospective study of 582 patients who had high frequency ultrasound examination was carried out. Those requiring more information on perfusion had colour doppler examination. Forty-four per cent of examinations were performed for scrotal swelling. The cause of the scrotal swelling was mainly extratesticular (75% of all scrotal swellings), hydrocele being the commonest. Of the intratesticular causes, infection (50.8%) and tumour (20.6%) were the commonest. In conclusion ultrasound examination distinguishes extratesticular (almost always benign) from intratesticular (potentially malignant) causes of scrotal swelling. Infection, trauma and torsion mimic the ultrasound appearance of tumour as do rare benign entities.

Treating men with predominantly nonpsychogenic erectile dysfunction with intracavernosal vasoactive intestinal polypeptide and phentolamine mesylate in a novel auto-injector system: a multicentre double-blind placebo-controlled study.

OBJECTIVE: To study the effect of intracorporeal injection (IC) of vasoactive intestinal polypeptide (VIP) and phentolamine mesylate (PM) on men with erectile dysfunction (ED) of nonpsychogenic aetiology. PATIENTS AND METHODS: The study comprised 236 men with primarily nonpsychogenic ED attending sexual dysfunction clinics at eight institutions. In an initial dose-assessment phase, the men were given IC injections of 25 micrograms VIP combined with PM 1.0 mg (VIP/P-1) or 2.0 mg (VIP/P-2) in a prefilled, single-use auto-injector. The main aetiologies of ED were arteriogenic (38), diabetes mellitus (DM) (39), neurogenic (35), mixed (90), and venous leakage (30). In a placebo-controlled phase, 171 patients were subsequently treated and self-administered up to 12 injections over a 6-month interval. RESULTS: In the dose-assessment phase there was an overall response rate of 82%, with responses by aetiology as follows: arteriogenic (82%), DM (85%), neurogenic (86%), mixed (80%), and venous leakage (77%). In a subgroup of 159 patients who withdrew from previous IC therapies for ED, 64% responded with an erection suitable for intercourse. Of the 171 patients treated in the placebo-controlled phase, 75% responded to VIP/P-1 and 12% to placebo (P<0.001); 66% responded to VIP/P-2 and 18% to placebo (P<0. 001), with a median duration of erection of 56 min. The principal adverse event was transient facial flushing accompanying 40% of 1711 injections. There was no pain after injection and one episode of priapism (0.06%); only seven patients withdrew because of adverse events. Over 88% and 92% of patients were satisfied with the drug and auto-injector, respectively. More than 85% of patients and 77% of partners reported an improved quality of life. CONCLUSION: The combination of VIP and PM at the dose used is a safe and effective means of treating male ED of primarily nonpsychogenic aetiology.

Vasoactive intestinal polypeptide and phentolamine mesylate administered by autoinjector in the treatment of patients with erectile dysfunction resistant to other intracavernosal agents.

OBJECTIVE: To study the effect of vasoactive intestinal polypeptide (VIP) and phentolamine mesylate (PM) on patients in whom previous intracavernosal therapy had failed. PATIENTS AND METHOD: The study comprised 70 consecutive patients attending a clinic for erectile dysfunction, in whom previous therapy with intracavernosal prostaglandin-E1 (20 microg and papaverine (30 mg) combined with 1 mg PM had failed. They were given intracavernosal injections, initially with 25 microg VIP/1 mg PM (VIP1) and if unsuccessful, 25 microg VIP/2 mg PM (VIP2). Both VIP1 and VIP2 were administered using a pre-filled ready-to-use autoinjector fitted with a 29 G needle. The patients were diagnosed as having spinal cord lesion (eight), diabetes (21), ischaemic heart disease (12), hypertension (six), other diagnoses (nine), or idiopathic causes (14). RESULT: Forty-seven (67%) of patients achieved erections sufficient for sexual intercourse (33 on VIP1 and 14 on VIP2), initially under clinical supervision and subsequently during home use. Minor side-effects were transient facial flushing in 37 (53%), truncal flushing in six (9%), bruising in 14 (20%) and pain from the injection needle in eight (11%). No patients reported priapism or other serious adverse events. CONCLUSION: The combination of VIP and PM at the dose used was a safe and effective treatment in patients in whom other therapies had failed.

A pilot study to investigate the treatment of anogenital warts with Topical Lithium Succinate cream (8% lithium succinate, 0.05% zinc sulphate).

The incidence of anogenital warts (condyloma acuminatum) is rapidly increasing while there is still no totally satisfactory treatment available. In light of the emphasis of experimental approaches toward the prevention of viral replication and evidence of the antiviral action of lithium salts it was proposed to investigate the efficacy of Topical Lithium Succinate cream (LSC) in the treatment of anogenital warts. A total of 101 patients (42 women, 59 men) were randomized to receive either active or placebo treatment for a period of 4 weeks. Assessment of the number, location, size and area of coverage of the warts was made by the clinician at baseline, weeks 2, 4, 6 and 12. Compliance to the study protocol following cessation of treatment at week 4 was extremely poor. The high drop-out rate after this was felt to invalidate data collected after that point. It was therefore decided that the analysis should concentrate on the treatment period. Of 101 patients entering the trial 51 received active (30 male and 21 female) and 50 received placebo (29 male, 21 female). The primary efficacy variable was percentage change from baseline in the overall coverage of lesions. Over all patients LSC treatment resulted in a reduction of 42% (P<0.02) in the overall coverage of lesions. Separate analyses for male and female patients showed that for males there was a highly significant reduction in the coverage of lesions of 65% (P<0.02). However for females the reduction of 11% was not significant. A possible explanation for this difference between the sexes is that as many of the lesions in the female patients were internal therefore this could lead to difficulty in both application of the cream, and subsequent lesion assessment.

Combined therapy trial with interferon alpha-2a and ablative therapy in the treatment of anogenital warts.

OBJECTIVE: To determine whether the combination of systemically administered interferon alpha-2a and ablative surgery for the treatment of genital and/or perianal warts produces a 30% or greater improvement in lasting response rate compared with a control group receiving a combination of placebo and ablative therapy. DESIGN: Randomised, triple-blind, placebo-controlled trial using 1 or 3 MIU of interferon alpha-2a or placebo administered subcutaneously three times weekly for 10 weeks in combination with ablative surgery. SETTING: International, multicentre study in 10 genitourinary medicine clinics. PATIENTS: Two hundred and fifty patients with anogenital warts. MAIN OUTCOME MEASURES: Lasting response at week 38. RESULTS: Standard efficacy analysis at week 38 showed a lasting response in 51% (35/68) of 3 MIU interferon-treated patients, 48% (30/63) of 1 MIU interferon-treated patients and 43% (29/67) of placebo-treated patients. CONCLUSIONS: With the doses and regime described, treatment with interferon alpha-2a in combination with ablative therapy is not significantly superior in the treatment of anogenital warts than placebo and ablative therapy.

Detection of human papilloma virus DNA sequences in oral squamous cell papillomas by the polymerase chain reaction.

Nineteen clinically diagnosed, and histologically confirmed oral squamous cell papillomas were analyzed for the presence of human papilloma virus DNA sequence by the highly sensitive polymerase chain reaction technique, followed by dot blot hybridization of the polymerase chain reaction product with digoxigenin-labeled, type-specific oligonucleotide probes for human papilloma virus DNA types 6, 11, 16, and 18. Human papilloma virus DNA types 6 and 11 were identified in 68% of these oral lesions, which raises the possibility of an etiologic role for human papilloma virus in the pathogenesis of oral squamous cell papillomas.

A randomised, double-blind, parallel group study to compare subcutaneous interferon alpha-2a plus podophyllin with placebo plus podophyllin in the treatment of primary condylomata acuminata.

OBJECTIVES: The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a (IFN) and podophyllin 25% W/V administered twice per week, preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule. The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups. DESIGN: Randomised, double-blind parallel group study. SETTING: Multicentre study in six genitourinary clinics within the U.K. PATIENTS: One hundred and twenty-four patients with primary anogenital warts. MAIN OUTCOME MEASURES: Complete response rate at week 10, and recurrence rate at week 26 in complete responders. RESULTS: At week 10 analysis of the efficacy population showed complete response in 36% (15/42 patients) of IFN-treated group and 26% (11/43 patients) in the placebo group (no significant difference). Analysis of the safety population at week 26 showed persistence of the complete response in 57% (8/14 patients) of the IFN-treated group and 80% (12/15 patients) of the placebo group (no significant difference). Adverse effects were more common in IFN-treated patients, involved particularly application site reaction and malaise but were generally mild. CONCLUSIONS: At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events.

The role of early colposcopy in the management of females with first episode anogenital warts.

212 females attending a genitourinary medicine (GUM) clinic with first episode anogenital warts were screened by cervical cytology and colposcopy/histology for the presence of cervical epithelial abnormalities in keeping with infection by the human papillomavirus (HPV infection) and/or cervical intraepithelial neoplasia (CIN). The prevalence of cervical epithelial abnormalities detected by cervical cytology alone was 32%, rising to 56% after colposcopic examination. However, the majority of cervical lesions detected by colposcopy alone were of low grade (HPV infection and/or CIN I). Histologically-confirmed high grade cervical lesions (CIN II or CIN III) were detected more frequently in those females in whom cervical cytological examination indicated dyskaryosis in keeping with any grade of CIN, compared to females without dyskaryotic changes on cervical smear (P < 0.05, chi-squared test with Yates' correction). Early colposcopy is indicated for females with anogenital warts in the presence of a cervical smear showing dyskaryosis in keeping with any grade of CIN, because of the statistically significant increased risk of detecting a potentially progressive high grade cervical lesion. In females without dyskaryotic changes on cervical smear, the value of early colposcopy is uncertain and warrants larger more long-term trials.

Detection of human papillomavirus by the polymerase chain reaction in histologically normal penile skin adjacent to penile warts.

BACKGROUND AND OBJECTIVES: Anogenital warts frequently recur following ablative treatment, and in the female, has been attributed to the presence of latent HPV infection outside the treatment margins. GOAL OF THIS STUDY: To determine whether HPV DNA sequences were detected by PCR in histologically normal penile skin adjacent to penile warts and to correlate recurrence of warts following surgical ablation to the presence of HPV DNA in histologically normal penile skin. STUDY DESIGN: Prospective cohort study of 25 heterosexual men with penile warts. Biopsies of clinically healthy penile skin 1 cm from the nearest penile lesion (wart with/without surrounding acetowhite changes) were processed for histology and HPV DNA analysis. The penile wart was processed for HPV DNA analysis only. Recurrence of penile warts was correlated to HPV status of adjacent histologically normal penile skin using Fisher's exact test (FET). RESULTS: Sequences homologous to HPV DNA were detected in 77% of biopsies of histologically normal penile skin. Agreement in HPV DNA type between penile wart and the adjacent histologically normal penile skin was only 30%. Recurrence of warts was noted in 46% of men by 16 weeks, and was not predicted by the detection of HPV DNA in the adjacent histologically normal penile skin (P = 0.16, FET). CONCLUSIONS: These findings suggest that extending the treatment margins 1 cm beyond the visible lesion is ineffective in eradicating the virus and preventing recurrence of warts.

Anogenital warts in children.

Fourteen children presenting with anogenital (AG) warts and their close family members were studied; 28.6 and 8.3% of presenting children and other child household members, respectively, had non-genital cutaneous warts; 42.8% of children with AG warts had one or more adult household member with common hand warts. Fifty per cent of all mothers had subclinical cervical papilloma virus (PV) infection; only one male adult had subclinical PV infection of the penis without concurrent AG warts. Of the children with AG warts 42.8% had one or more adult household member with AG warts. Human papilloma virus (HPV) deoxyribonucleic acid (DNA), type 6/11 most frequently, was detected in 38.5% AG wart biopsies from children, and 67% AG wart biopsies from adults. HPV 31/33/35 was detected in 28.5% of cervical preneoplasias and type 6/11 in the one case of subclinical PV infection of the penile shaft. Detection of HPV types 6/11, 16/18, or 31/33/35 in AG warts in children was significantly associated with vertical (from an HPV-infected maternal birth canal during vaginal delivery) or sexual transmission of these warts (Fisher exact probability P = 0.031).

Human papillomavirus DNA detection in primary anogenital warts and cervical low-grade intraepithelial neoplasias in adults by in situ hybridization.

In this study, 58 consecutive patients with primary anogenital warts were selected from patients attending a genitourinary clinic. Patients were grouped on the basis of clinical lesion site, i.e. patients with genital warts only, patients with perianal or anal canal warts only, and patients with concurrent perianal and genital warts. Of these patients, 38% of the men (12/31) and 33.3% of the women (9/27) had other anogenital infections, such as nonspecific urethritis (NSU) or nonspecific genital infection, which were the most common. Of the patients who had perianal warts, 37% of the men (7/19) and 25% of the women (4/16) also had warts in the anal canal. Of the women who had anogenital warts, 63% (17/27) had concurrent subclinical low-grade cervical intraepithelial neoplasia (CIN) lesions. Human papilloma virus (HPV) DNA (either 6 or 11, 16 or 18, or 31 or 33 or 35) was detected in 53.3% (40/75) of the anogenital wart biopsy samples, and in 35.2% (6/17) of the low-grade CIN lesions. HPV types 6 or 11 were the most common types in anogenital warts (45.3%); and in CIN lesions HPV types 6 or 11 and 16 or 18 were found with equal frequency (17.6% each). There were no significant differences in HPV types between patients with genital warts and patients with perianal and anal canal warts. Anogenital infection with HPV is multicentric; external anogenital warts and subclinical CIN lesions often exist concurrently. The low prevalence of HPV DNA detected in anogenital warts and CIN biopsy samples may be due to insensitivity of the in situ hybridization technique used in this study.

A placebo controlled observer blind immunocytochemical and histologic study of epithelium adjacent to anogenital warts in patients treated with systemic interferon alpha in combination with cryotherapy or cryotherapy alone.

OBJECTIVE: To examine biopsy specimens of tissue immediately adjacent to anogenital (AG) warts which had been treated with either cryotherapy plus subcutaneous interferon (IFN) alpha 2a or cryotherapy alone, for histological features of (a) human papilloma virus (HPV) infection (b) localised cellular immune responses, to further characterise any cellular immune infiltrates with tissue immunocytochemistry, and to relate any histological, immunocytochemical findings to the treatment response of nearby AG warts. DESIGN: A randomised placebo controlled observer blind study. SETTING: Genitourinary Medicine clinic, Department of Immunopathology, Royal Victoria Hospital, Belfast, N. Ireland. SUBJECTS: Thirty patients with AG warts; 16 treated with IFN alpha 2a plus cryotherapy, and 14 treated with cryotherapy alone. OUTCOME MEASURES: (1) Light microscopic features associated with HPV infection and local cellular immune responses. (2) Indirect immunofluorescence detection of the following cell surface markers: HLA DR, alpha one antitrypsin, CD1, CD3, CD4, CD8, CD22. (3) Clinical response of AG warts to treatment. RESULTS: In pre-treatment biopsies only non specific indicators of HPV infection (acanthosis, 29/30 biopsies, and hyperkeratosis, 7/30 biopsies) were seen on light microscopy. Mononuclear cells were seen both throughout the upper dermis and centred around dermal blood vessels in 19/30 (63.3%) biopsies, and infiltrating into the epidermis in 12/30 (40%) biopsies. On indirect immunofluorescence CD3, CD8, CD4 antigen was detected on the surface of cells throughout the upper dermis in 24/29 (82.7%), 15/29 (51.7%), and 3/29 (10.3%), of biopsy specimens respectively. CD3 antigen, CD8 antigen and CD4 antigen was detected on the surface of cells infiltrating into the epidermis in 18/29 (62%), 7/29 (24.1%), and 6/29 (20.7%) of biopsy specimens respectively. CD1 antigen was seen on the surface of dendritic cells throughout the epidermis in all specimens; CD1 positive cells infiltrated into the upper dermis in 5/29 (17.2%). HLA DR was detected on the surface of dendritic cells throughout the epidermis in 22/29 (75.9%) of specimens, and on the surface of cells scattered both diffusely throughout the upper dermis and centred around dermal blood vessels in all specimens. Alpha one antitrypsin (A1AT) antigen was seen on the surface of cells in the upper dermis in 6/29 (20.7%) of biopsy specimens; no cells expressing CD22 surface antigen were seen. The nature of this local cellular immune response was not altered by treatment of nearby warts with either cryotherapy alone or cryotherapy plus systemic IFN alpha 2a, or related to the therapeutic outcome of these warts. CONCLUSIONS: (1) No convincing histological evidence of HPV infection was seen in epithelium surrounding AG warts. (2) A predominantly T cell-mediated immune response (the target of which is uncertain) was seen in this perilesional epithelium. (3) In the dosage regimens used in this study, treatment of AG warts with either systemic IFN alpha 2a plus cryotherapy or cryotherapy alone did not appear to augment localised cellular immune responses (against any presumed subclinical HPV infection) in epithelium surrounding AG warts.