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1.  A study of 113 cases of genital ulcerative disease and urethral discharge syndrome with validation of syndromic management of sexually transmitted diseases 
Aims:
To validate syndromic management of cases having genital ulcerative disease (GUD) and urethral discharge syndrome (UDS).
Materials and Methods:
A study of 113 cases of GUD and UDS was carried out in the Department of Skin and VD from March 2011 to August 2012. All cases having history and clinical evidence suggestive of GUD and UDS were included in the study.
Results:
According to syndromic diagnosis, GUD herpetic syndrome was the most common 71 (62.27%), followed by GUD non-herpetic syndrome 25 (21.89%) and UDS 17 (14.91%). Out of 71 cases clinically diagnosed as GUD herpetic, 16 (22.53%) were validated by immunoglobulin M (IgM) anti herpes simplex virus-2 (HSV) serology, 14 (19.71%) by Tzanck smear and 3 (4.22%) by both. 24 (33.80%) were Reactive plasma Reagin (RPR)(<1:8) reactive and trepenomma palidum haem-agglutination positive. Out of total 25 clinically diagnosed GUD non herpetic cases, 22 (88%) were validated by laboratory tests Out of 17 cases of UDS, 15 (88%) were validated by smear.
Conclusion:
Sensitivity and specificity of clinically diagnosed syndrome is not so high particularly for GUD herpetic syndrome Continuous monitoring of diagnostic component of syndromic approach is key to success of STD control program.
doi:10.4103/0253-7184.132426
PMCID: PMC4066595  PMID: 24958984
Genital ulcer disease; syndromic management; urethral discharge syndrome; validation
2.  Coexistence of urethritis with genital ulcer disease in South Africa: influence on provision of syndromic management 
Sexually Transmitted Infections  2002;78(4):274-277.
Objective: To assess whether syndromic management of genital ulcer disease was sound, if based on the premise that men with genital ulcers rarely have a concomitant urethral infection.
Methods: Specimens were taken in 1998 from 186 mine workers in Carletonville, South Africa, who were seen consecutively with genital ulcers. The specimens comprised a swab from the ulcer, a urethral swab for a Gram stained smear, and 10–15 ml of a first catch urine sample. The latter was tested by ligase chain reaction assays for Neisseria gonorrhoeae and Chlamydia trachomatis specific DNA sequences and by a polymerase chain reaction (PCR) assay for Mycoplasma genitalium. Ulcer inducing micro-organisms were detected either by a multiplex PCR assay, or in the case of lymphogranuloma venereum (LGV) serologically, and human immunodeficiency virus (HIV) infection was detected by an enzyme linked immunosorbent assay (ELISA) test.
Results: Most (54%) of the ulcers were chancroidal, 18% were herpetic (HSV type 2), 6.5% primary syphilitic, and 3.2% due to LGV. More than one micro-organism was detected in 9.1% of the ulcers and less than 10% were undiagnosed. Microscopic examination of the urethral smears showed that 99 (53%) of the men had urethritis, of whom 45 (45%) were infected with N gonorrhoeae. Of the 54 men (55%) who had non-gonococcal urethritis (NGU), 11 (19.6%) harboured C trachomatis or M genitalium. Almost two thirds (64.5%) of the men had HIV infection, but this did not seem to have influenced the aetiology of the ulcers. Nor was a particular ulcer associated with one type of urethritis more than the other. Neither C trachomatis nor M genitalium was associated significantly with non-gonococcal urethritis (NGU) in either HIV positive or HIV negative men.
Conclusion: The combination of antibiotics used for the management of genital ulcer disease in men in this South African mining population needs to be widened to encompass frequently occurring concomitant gonococcal urethritis and NGU infections. This means treatment with long acting penicillin, combined with ciprofloxacin and azithromycin or erythromycin. A similar situation may exist in other geographical locations with a need to provide appropriate antimicrobial combinations depending on the patterns of infection detected.
doi:10.1136/sti.78.4.274
PMCID: PMC1744505  PMID: 12181466
3.  Herpetic keratitis in Tanzania: association with malaria. 
Of 103 patients who presented to a rural clinic in Africa with corneal ulceration, 62 (60.2%) had corneal ulcers which on clinical diagnosis were attributable to herpes simplex virus. There was a strong association between herpetic ulceration and a history of recent malaria; 37 of 62 (59.7%) herpetic ulcers occurred in the 3 month period from April to June which corresponds to the end of the peak season for malaria compared with 14 of 41 (34%) of the non-herpetic ulcers. Fifty per cent of herpetic ulcers had a geographic morphology, 27.4% were dendritic, and 22.6% presumed herpetic ulcers were stromal: 38.7% of herpetic ulcers occurred in children under 5 years of age. Bilateral herpetic ulcers occurred in 16.1% of patients but were more common in children under 2 years of age. Geographic and stromal ulcers tended to heal more slowly than dendritic ulcers (mean time to healing 12.6, 12.2, and 6.6 days respectively), and were more likely to result in severe corneal scarring (45%, 29%, and 0% respectively). Herpes simplex keratitis is a major cause of corneal scarring in Africa. It is often seen in children, may be bilateral, commonly is geographic in morphology, and has a strong association with malaria infection. Because it is not easily preventable, more effort must be made to ensure early diagnosis and prompt, effective treatment in order to prevent severe scarring and visual loss.
Images
PMCID: PMC505219  PMID: 1420038
4.  Magnetic resonance imaging of solid urethral and peri-urethral lesions 
Insights into Imaging  2013;4(4):461-469.
Solid urethral and peri-urethral lesions are rare and encompass benign and malignant aetiologies. A diagnosis without imaging is often challenging secondary to non-specific clinical symptoms and overlapping findings at the time of physical examination. Magnetic resonance (MR) imaging may be helpful in confirming a diagnosis while providing anatomical detail and delineating disease extent. This article reviews the normal MR anatomy of the male and female urethra, the MR appearance of solid primary and secondary urethral lesions, and the MR appearance of solid urethral lesion mimics.
Teaching points
• MRI is an important imaging technique in the evaluation of the spectrum of solid urethral lesions.
• With excellent soft tissue resolution, MR is accurate in staging primary urethral carcinoma.
• Disruption of the zonal anatomy of the female urethral wall indicates peri-urethral extension.
• Be aware of benign urethral lesions, particularly those that may mimic solid urethral masses.
doi:10.1007/s13244-013-0259-3
PMCID: PMC3731464  PMID: 23686749
Urethra; Carcinoma; Magnetic resonance; Solid lesions
5.  SONOURETHROGRAPHY IN THE EVALUATION OF ANTERIOR URETHRAL STRICTURE  
Abstract
Background
The management of urethral stricture is a challenge to both the urologists and the patients. Thoughtful and satisfactory preoperative evaluation remains important to achieving good outcome. Retrograde urethrography and Micturating Cystourethrography (RUG/MCUG) have been the gold standard imaging technique in the evaluation of anterior urethral stricture but are not without inherent limitations and side effects. Sonourethrography (SUG) could diagnose anterior urethral stricture, measure its length, and detect presence of complications and extent of spongiofibrosis
Aims and Objectives
To establish the sensitivity of sonourethrography in the identification of the anterior urethral stricture.
To determine the accuracy of sonourethrography in measuring the length of anterior urethral stricture as well as to detecting spongiofibrosis.
Patients and Methods
This was a prospective study of 60 patients clinically diagnosed to have anterior urethral stricture. The patients included in the study underwent both SUG and RUG/MCUG. The sensitivity of SUG was then calculated. Paired t-test was used to determine its ability to measure the length of the anterior urethral stricture. The percentage of patients detected to have spongiofibrosis on SUG was also computed.
Results
The mean age of patients recruited for the study was 46 ± 18 years (Range = 9-69). The sensitivity of SUG was 94%. The lengths of anterior urethral stricture were 14.1 ± 1.9mm and 16.0 ± 2.1mm for RUG/MCUG and SUG respectively. The mean difference is 2.0mm (Confidence interval, CI = 0.872 – 2.911, p<0.05). SUG correctly identified spongiofibrosis in 31(51.7%) patients that had anterior urethral stricture.
Conclusion
This study has demonstrated that sonourethrography is a valuable diagnostic tool in the evaluation of anterior urethral stricture.
PMCID: PMC4170287  PMID: 25452974
6.  Racial Differences in the Structure and Function of the Stress Urinary Continence Mechanism 
Obstetrics and gynecology  2000;95(5):713-717.
Objective
To compare the structure and function of the urethral sphincter and the urethral support in nulliparous black and white women.
Methods
Eighteen black women (mean age 28.1 years) and 17 white women (mean age 31.3 years) completed this cross-sectional study. The following assessments were made: urethral function using multichannel cystometrics and urethral pressure profilometry, pelvic muscle strength using an instrumented speculum, urethral mobility using the cotton-swab test and perineal ultrasound, and pelvic muscle bulk using magnetic resonance imaging.
Results
Black women demonstrated a 29% higher average urethral closure pressure during a maximum pelvic muscle contraction (154 cm H2O versus 119 cm H2O in the white subjects; P = .008). Although not statistically significant, black women had a 14% higher maximum urethral closure .23) and pressure at rest (108 cm H2O versus 95 cm H2O; P = a 21% larger urethral volume (4818 mm3 versus 3977 mm3; P = .06). In addition, there was a 36% greater vesical neck mobility measured with the cotton-swab test (blacks 49° versus whites 36°; P = .02) and a 42% difference in ultrasonically measured vesical neck mobility during a maximum Valsalva effort (blacks = −17 mm versus whites −12 mm; P = .08).
Conclusion
Functional and morphologic differences exist in the urethral sphincteric and support system of nulliparous black and white women.
PMCID: PMC1283097  PMID: 10775735
7.  The UREThRAL stricture score: A novel method for describing anterior urethral strictures 
Background:
Urethral stricture description is not standardized. This makes surgical decision-making less reproducible and increases the difficulty of objectively analyzing urethroplasty literature. We developed a standardized system, the UREThRAL stricture score (USS), to quantify the characteristics of anterior urethral stricture disease based on preoperative imaging and intraoperative findings.
Methods:
To develop the USS, we retrospectively analyzed 95 consecutive patients with urethral strictures who underwent open urethroplasty by a single surgeon (SBB) at Barnes-Jewish Hospital from 2009 to 2011. The USS is a numerical score based on five components of anterior urethral stricture disease that help dictate operative decision-making: (1) (UR)ethral stricture (E)tiology; (2) (T) otal number of strictures; (3) (R)etention (luminal obliteration); (4) (A)natomic location; and (5) (L)ength. Stricture management was categorized by increasing surgical complexity: excision/primary anastomosis (EPA), buccal mucosal graft urethroplasty (BMG), augmented anastomotic urethroplasty (AAU), flap urethroplasty, and a combination of flaps and/or grafts. Multinomial logistic regression analysis was used to compare USS to surgical complexity.
Results:
The mean USS for EPA, BMG, AAU, flap, and combination flaps/grafts was 5.78, 8.82, 9.23, 11.01, and 14.97, respectively. Increasing USS was significantly associated with surgical complexity (p < 0.0001).
Interpretation:
The USS describes the essential factors in determining surgical treatment selection for urethral stricture disease. The USS is a concise, easily applicable system that delineates the clinically significant features of urethral strictures. Valuable comparison of anterior urethral stricture treatments in clinical practice and in the urological literature could be facilitated by using this novel UREThRAL stricture score.
doi:10.5489/cuaj.12048
PMCID: PMC3433541  PMID: 23093535
8.  Novel insight into the dynamics of male pelvic floor contractions through transperineal ultrasound imaging 
The Journal of urology  2012;188(4):1224-1230.
Purpose
Transperineal ultrasound imaging (US) enables minimally invasive assessment of pelvic floor muscle function. Although commonly used in females, the approach has not been reported in males. This approach has advantages because the mid-sagittal view visualises a bony landmark and the entire urethral length. This allows investigation of displacement of multiple points along the urethra and the unique mechanical actions of multiple muscles that could influence continence. We used a new transperineal US technique to compare relative displacement of urethra-vesical junction, ano-rectal junction, and distal urethra during voluntary pelvic floor muscle contractions in continent men.
Materials and Methods
Measurement and comparison of urethral displacement at specific urethral regions in ten continent males (28-41 years). Measures made on 2D mid-sagittal plane ultrasound images included the displacements of specific points along the urethra. Anatomic considerations suggest that these are caused by contraction of the levator ani, striated urethral sphincter and bulbocavernosus muscles. Pearson's correlation coefficient was used in investigate the relationship between displacements of pairs of points.
Results
Data show individual variation in displacement of the distal urethra (striated urethral sphincter contraction) and urethra-vesical junction (levator ani contraction). A strong inverse linear relationship (0.723) between displacements of these points indicates two alternative strategies of urethral movement.
Conclusions
Transperineal US imaging allows simultaneous investigation of multiple pelvic floor muscles by measurement of urethral displacement. Data provide evidence of different but coordinated strategies of urethral displacement in males.
doi:10.1016/j.juro.2012.06.028
PMCID: PMC4106154  PMID: 22902016
perineal; ultrasound imaging; male continence; striated urethral sphincter; urinary incontinence
9.  Tzanck smear in diagnosing genital herpes. 
Genitourinary Medicine  1988;64(4):249-254.
In 126 patients with anogenital lesions, in which herpes simplex virus (HSV) infection was suspected or included in the differential diagnosis, the results of cytodiagnosis of herpetic infection (Tzanck smear) were compared with virus culture. Cervical lesions were excluded from this study. HSV infection was proved by culture in 78 patients and was absent or non-active in 41 patients. Excluded from this study were seven patients who did not yield the virus on culture but had positive Tzanck smear results from three investigators. The characteristic cytopathic effect of herpetic infection was found in 78 patients who yielded HSV on culture. Tzanck smear sensitivity for skin lesions was 79% and for mucous membrane lesions was 81% in men and 52% in women. Tzanck smear specificity for the 41 patients without herpetic infection proved by virus culture was 93%. Differences in sensitivity and specificity between the results found by three investigators (double blind screening) were not significant. The Tzanck smear is reliable, inexpensive, and easy and quick to perform; it is suitable for office diagnosis because it does not require a specialised laboratory.
Images
PMCID: PMC1194227  PMID: 3169755
10.  Efficacy of acycloguanosine against herpetic ulcers in rabbit cornea. 
The effect of a new antiherpetic compound of very low toxicity called acycloguanosine (Wellcome 248U) on herpetic ulcers in rabbit cornea was studied by the Corneal Epithelial Lesion Therapeutic Assay (CELTA). The therapeutic effect of 3% acycloguanosine ointment on dendritic ulcers was equal to that of 0.5% 5-iodo-2'-deoxyuridine (IDU) ointment. No toxic symptoms could be detected by slit-lamp on 4 days' treatment with this concentration of acycloguanosine. Because of its selective action on virus only, its extremely low toxicity in animals, and its availability for systemic administration, acycloguanosine seems to be an ideal antiviral compound for use in the treatment not only of herpetic keratitis but also of other herpetic diseases in man.
Images
PMCID: PMC1043503  PMID: 465415
11.  Acute follicular conjunctivitis and keratoconjunctivitis due to herpes simplex virus in London. 
During the 18 months January 1975 to June 1976, 25 cases of acute herpetic follicular conjunctivitis and keratoconjunctivitis resembling adenovirus ocular infection presented in the External Eye Disease Clinic, Moorfields Eye Hospital, City Road, London. Herpes simplex virus was isolated in HEp2 cells in 22 patients, and the remaining 3 patients were identified by a minimum 4-fold rise in the level of antiherpes simplex virus antibody in their blood. No adenovirus was isolated from these patients, but complement fixation test for adenovirus was positive in 1 patient with cultural test positive for herpes simplex virus. Most patients were between 20 and 35 years old and the ratio of males to females was 12 to 13. At the initial visit the clinical features of disease were moderate to severe conjunctival papillary and follicular reasons with epithelial and subepithelial punctate keratitis but little systemic disease. In the absence of typical herpetic lesions of face, lids, or cornea the disease resembled adenovirus types 8 or 19 keratoconjunctivitis. Of these 25 patients 5 subsequently developed typical herpetic lesions of lids or cornea. In the remaining 20 cases the correct diagnosis could be made only by cultural or serological tests. Virological diagnosis provides a rational basis for antiherpetic chemotherapy, which appears to shorten the course of infection.
Images
PMCID: PMC1043370  PMID: 737165
12.  La mammillite herpétique bovine au Québec 
The Canadian Veterinary Journal  1987;28(8):529-532.
Bovine herpetic mammillitis in Quebec
Bovine herpetic mammillitis is reported for the first time in Canada. It is a vesicular and ulcerative skin disease affecting the udder and teats of cows. It is caused by the bovine herpesvirus 2. The principal lesions consist of crusts that are found on the teats and may become complicated by secundary bacterial infection.Specimens collected from the lesions were used to differentiate the condition from pseudo-cowpox by serological tests, virus isolation and electron microscopy. Bovine herpetic mammillitis causes painful and therefore difficult milking which is followed by mastitis and an increased rate of culling.
Images
PMCID: PMC1680612  PMID: 17422846
Bovine; mammillitis; teat; bovine herpesvirus 2
13.  The Surgical Procedure Is the Most Important Factor Affecting Continence Recovery after Laparoscopic Radical Prostatectomy 
The World Journal of Men's Health  2013;31(2):163-169.
Purpose
We analyzed factors associated with early recovery of continence after laparoscopic radical prostatectomy.
Materials and Methods
Among 467 patients treated with laparoscopic radical prostatectomy for localized prostate cancer between 2007 and 2012, 249 patients who underwent a preoperative urodynamic study were enrolled. The patients' age, prostate volume, preoperative serum prostate-specific antigen (PSA), Gleason score, pathologic stage, and preoperative urodynamic parameters were recorded. The preoperative membranous and prostatic urethral length on magnetic resonance image, nerve sparing technique, and type of surgical procedure (extrafascial and intrafascial) were analyzed. Patients were considered to have early recovery of continence when they needed no pad in 3 months or less after surgery.
Results
Ninety-two patients were in the early recovery group and 157 were in the late recovery group. The membranous urethral lengths were 12.06±2.56 and 11.81±2.87 mm, and prostatic urethral lengths were 36.39±6.15 and 37.45±7.55 mm in each group, respectively. The membranous-posterior urethral length ratios were 0.25±0.06 and 0.24±0.06, and prostatic-posterior urethral length ratios were 0.75±0.06 and 0.76±0.06, respectively. In and of themselves, the membranous and prostatic urethral lengths were not associated with recovery duration however, the membranous-total and prostatic-total urethral length ratios were related (p=0.024 and 0.024, respectively). None of the urodynamic parameters correlated with continence recovery time. In the multivariate analysis, the type of surgical procedure (odds ratio [OR], 7.032; 95% confidence interval [CI], 2.660 to 18.590; p<0.001) and membranous urethral length (OR, 0.845; 95% CI, 0.766 to 0.931; p=0.001) were significantly related to early recovery of continence.
Conclusions
The current intrafascial surgical procedure is the most important factor affecting early recovery of continence after laparoscopic radical prostatectomy.
doi:10.5534/wjmh.2013.31.2.163
PMCID: PMC3770852  PMID: 24044112
Laparoscopy; Prostatic neoplasms; Urinary incontinence
14.  Human papillomavirus DNA in the urogenital tracts of men with gonorrhoea, penile warts or genital dermatoses. 
Genitourinary Medicine  1993;69(3):187-192.
OBJECTIVE--To assess the presence of human papillomavirus (HPV) DNA in urethral and urine specimens from men with and without sexually transmitted diseases. DESIGN--Prospective study. SETTING--Two London departments of genitourinary medicine PATIENTS--100 men with urethral gonorrhoea, 31 men with penile warts and 37 men with genital dermatoses. METHODS--Urethral and urine specimens were taken, HPV DNA extracted and then amplified using the polymerase chain reaction. HPV types 6, 11, 16, 18, 31 and 33 were identified using Southern blotting followed by hybridisation. RESULTS--HPV DNA was detected in 18-31% of urethral swab specimens and in 0-14% of urine specimens. Men with penile warts had HPV detected in urethral swabs more often than did men in the other two clinical groups. "High risk" HPV types were found in 71-83% of swab specimens and in 73-80% of urine specimens containing HPV DNA. CONCLUSIONS--HPV is present in the urogenital tracts of men with gonorrhoea, penile warts and with genital dermatoses. In men with urethral gonorrhoea, detection of HPV in urethral specimens is not related to the number of sexual partners, condom usage, racial origin or past history of genital warts. HPV DNA in the urethral swab and urine specimens may represent different aspects of the epidemiology of HPV in the male genital tract. The preponderance of HPV types 16 and 18 in all three groups of men may be relevant to the concept of the "high risk male".
Images
PMCID: PMC1195060  PMID: 8392967
15.  Topical ganciclovir in the treatment of acute herpetic keratitis 
Herpetic keratitis is caused by herpes simplex virus (HSV) and is a common cause of corneal blindness. Following a primary ocular herpetic infection, latency of the virus occurs, followed by subsequent recurrences of herpetic keratitis. Such recurrences may lead to structural damage of the cornea. Recurrent herpetic keratitis is a common indication for corneal transplantation. Recurrences of herpetic keratitis in the corneal graft may lead to corneal graft rejection. Several antiviral agents for HSV are available, including the thymidine analogs. Prolonged use of thymidine analogs may lead to toxicity of the ocular surface, including epithelial keratitis, corneal ulcers, follicular conjunctivitis, and punctal occlusions. Availability of topical antiviral agents that are safe and effective in the treatment and prophylaxis of herpetic keratitis is highly desirable. Ganciclovir is a potent inhibitor of members of the herpes virus family. The drug has been used systemically for the treatment of cytomegalovirus (CMV) retinitis. Its hematologic toxicity secondary to systemic administration led to its limited use in herpetic infections. On the other hand, topical ganciclovir has been shown to be as safe and effective as acyclovir in the treatment of herpetic epithelial keratitis. Furthermore, topical ganciclovir can reach therapeutic levels in the cornea and aqueous humor following topical application. Several clinical trials have shown that topical ganciclovir 0.15% ophthalmic gel is safe and effective in the treatment and prophylaxis of herpetic epithelial disease. Long-term use of ganciclovir ophthalmic gel in patients with penetrating keratoplasty following herpetic keratitis has prevented recurrences of the disease. Topical ganciclovir ophthalmic gel is well tolerated, does not cause toxic effects on the ocular surface, and does not cause hematologic abnormalities. Clinical studies have underscored the potential role of ganciclovir ophthalmic gel in the treatment and prophylaxis of herpetic epithelial keratitis. Future randomized, controlled, multicenter, prospective clinical trials are needed to assess the long-term safety and efficacy of topical ganciclovir in the treatment and prevention of herpetic keratitis and uveitis.
PMCID: PMC2925452  PMID: 20823931
herpetic keratitis; cornea; herpes simplex; ganciclovir; acyclovir
16.  Herpes Zoster Vaccine Effectiveness against Incident Herpes Zoster and Post-herpetic Neuralgia in an Older US Population: A Cohort Study 
PLoS Medicine  2013;10(4):e1001420.
Sinead Marie Langan and colleagues studied a cohort of more than 750,000 individuals over the age of 65 years to assess whether herpes zoster vaccine is effective against incident zoster and post-herpetic neuralgia in an older population.
Background
Herpes zoster is common and has serious consequences, notably post-herpetic neuralgia (PHN). Vaccine efficacy against incident zoster and PHN has been demonstrated in clinical trials, but effectiveness has not been studied in unselected general populations unrestricted by region, full health insurance coverage, or immune status. Our objective was to assess zoster vaccine effectiveness (VE) against incident zoster and PHN in a general population-based setting.
Methods and Findings
A cohort study of 766,330 fully eligible individuals aged ≥65 years was undertaken in a 5% random sample of Medicare who received and did not receive zoster vaccination between 1st January 2007 and 31st December 2009.
Incidence rates and hazard ratios for zoster and PHN were determined in vaccinated and unvaccinated individuals. Analyses were adjusted for age, gender, race, low income, immunosuppression, and important comorbidities associated with zoster, and then stratified by immunosuppression status. Adjusted hazard ratios were estimated using time-updated Cox proportional hazards models.
Vaccine uptake was low (3.9%) particularly among black people (0.3%) and those with evidence of low income (0.6%). 13,112 US Medicare beneficiaries developed incident zoster; the overall zoster incidence rate was 10.0 (9.8–10.2) per 1,000 person-years in the unvaccinated group and 5.4 (95% CI 4.6–6.4) per 1,000 person-years in vaccinees, giving an adjusted VE against incident zoster of 0.48 (95% CI 0.39–0.56). In immunosuppressed individuals, VE against zoster was 0.37 (95% CI 0.06–0.58). VE against PHN was 0.59 (95% CI 0.21–0.79).
Conclusions
Vaccine uptake was low with variation in specific patient groups. In a general population cohort of older individuals, zoster vaccination was associated with reduction in incident zoster, including among those with immunosuppression. Importantly, this study demonstrates that zoster vaccination is associated with a reduction in PHN.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Chickenpox is an extremely common childhood infectious disease that is caused by the herpes varicella-zoster virus. Children usually recover quickly from chickenpox, but dormant varicella-zoster virus persists throughout life inside the nervous system. The dormant virus causes no symptoms but if it becomes reactivated, it causes shingles (zoster), a painful skin rash. Anyone who has had chickenpox can develop shingles but shingles is most common and most severe in 60–80-year-old people. Indeed, about half of people who live to 85 will have an episode of shingles. Early signs of shingles include burning or shooting pain and tingling or itching. Blister-like sores, which last from 1–14 days, then develop in a region of one side of the body or on one side of the face. The pain of shingles can be debilitating and can continue after the rash disappears—“post-herpetic neuralgia,” which can last for months to years, greatly reduces the quality of life. There is no cure for shingles but early treatment with antivirals may help to prevent lingering pain by inhibiting viral replication.
Why Was This Study Done?
Shingles vaccination can prevent shingles or lessen its effects. In clinical trials, vaccination reduced the incidence of shingles (the proportion of a population who develop shingles in a year) and the incidence of post-herpetic neuralgia, and vaccination against shingles is now recommended in the US for everyone over the age of 60 except individuals with a weakened immune system (for example, people with HIV/AIDS). However, these clinical trials determined the vaccine's efficacy in selected populations under controlled conditions. How effective is the vaccine in unselected populations in routine clinical use? In this cohort study, the researchers assess zoster (shingles) vaccine effectiveness against incident shingles and post-herpetic neuralgia in an unselected population of older individuals in the US. A cohort study follows a group of individuals who differ with respect to specific factors (in this study, vaccination against shingles) to determine how these factors affect the rates of specific outcomes (shingles and post-herpetic neuralgia).
What Did the Researchers Do and Find?
The researchers undertook their cohort study in 766,330 randomly chosen Medicare beneficiaries aged 65 years or more. Medicare is a US government health insurance scheme that mainly helps to pay the health care costs of people aged 65 or older. The researchers used Medicare administrative data to identify which cohort members received zoster vaccination between January 2007 and December 2009 and which developed incident shingles (defined as a first diagnosis of shingles combined with the use of antivirals) or post-herpetic neuralgia (defined as a code for post-herpetic neuralgia, non-specific neuralgia, or a second diagnostic code for shingles 90 days after the first diagnosis combined with a prescription for pain relief, an anticonvulsant, or an antidepressant). Vaccine uptake was low in this unselected study population—only 3.9% of the participants were vaccinated. The vaccination rate was particularly low among black people (0.6% of person-time) and among people with a low income (0.3%). About 13,000 participants developed incident shingles. The shingles incidence rate was 10.0 per 1,000 person-years among unvaccinated participants and 5.4 per 1,000 person-years among vaccinated participants. Vaccine effectiveness against incident shingles was 48%. That is, vaccination reduced the incidence of shingles by 48% (in other words, approximately half as many vaccinated individuals developed shingles as those who were not vaccinated). Vaccine effectiveness against incident shingles among immunosuppressed individuals was lower (37%). Finally, vaccine effectiveness against post-herpetic neuralgia was 59%.
What Do These Findings Mean?
These findings show that shingles vaccine uptake is low among elderly people in the US and varies between different patient groups. They show that shingles vaccination is effective against incident shingles in a general population of older individuals, including those who are immunosuppressed, and suggest that shingles vaccination is effective against post-herpetic neuralgia. However, because these findings rely on administrative data, their accuracy may be affected by misclassification of vaccination and of outcomes. Moreover, because shingles vaccination was not randomized, the vaccinated individuals might have shared other characteristics that were actually responsible for their lower incidence of shingles and/or post-herpetic neuralgia compared to unvaccinated individuals. Despite these limitations, these findings provide useful information for policy makers in countries that are currently considering the introduction of shingles vaccination into routine practice. Moreover, they highlight the need to increase shingles vaccination among elderly individuals in the US, the section of the population at the highest risk of post-herpetic neuralgia.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1001420.
The US Centers for Disease Control and Prevention have detailed information about all aspects of shingles (zoster), including information on vaccination for the public and for health care professionals, and a personal story about shingles
The NIH Senior Health website includes information on shingles and a video describing a personal experience of shingles
The UK National Health Service Choices also provides information about all aspects of shingles and a personal story
MedlinePlus provides links to other resources about shingles (in English and Spanish)
The British Association of Dermatologists website has an information leaflet on shingles
The New Zealand Dermatological Society website has a leaflet on shingles
doi:10.1371/journal.pmed.1001420
PMCID: PMC3621740  PMID: 23585738
17.  Microtomographic Analysis of Lower Urinary Tract Obstruction 
Prenatal obstruction of the lower urinary tract may result in megacystis, with subsequent development of hydro-ureter, hydronephrosis, and renal damage. Oligo- or anhydramnios, pulmonary hypoplasia, and prune belly syndrome are lethal consequences. Causes and mechanisms responsible for obstruction remain unclear but might be clarified by anatomic study at autopsy. To this end, we employed 2 methods of tomographic imaging—optical projection tomography and contrast-enhanced microCT scanning—to elucidate the anatomy of the intact urinary bladder and urethra in 10 male fetuses with lower urinary tract obstruction. Images were compared with those from 9 age-matched controls. Three-dimensional images, rotated and sectioned digitally in multiple planes, permitted thorough examination while preserving specimens for later study. Both external and internal features of the bladder and urethra were demonstrated; small structures (ie, urethral crest, verumontanum, prostatic utricle, ejaculatory ducts) were seen in detail. Types of obstruction consisted of urethral atresia (n = 5), severe urethral stenosis (n = 2), urethral diaphragm (n = 2), or physical kinking (n = 1); classic (Young type I) posterior urethral valves were not encountered. Traditional light microscopy was then used to verify tomographic findings. The prostate gland was hypoplastic or absent in all cases; in 1, prostatic tissue was displaced inferior to the verumontanum. Findings support previous views that dissection may produce valve-like artifacts (eg, bisection of an obstructing diaphragm) and that deformation of an otherwise normal urethra may result in megacystis. The designation “posterior urethral valves” should not be used as a generic expression of urethral obstruction unless actual valves are demonstrated.
doi:10.2350/13-08-1359-OA.1
PMCID: PMC3965709  PMID: 23977847
lower urinary tract obstruction; microCT scanning; optical projection tomography; posterior urethral valves; prune belly syndrome; urethral atresia
18.  Urethral metastasis from a sigmoid colon carcinoma: a quite rare case report and review of the literature 
BMC Surgery  2014;14:31.
Background
Urethral metastatic adenocarcinoma is extremely rare. Moreover, only 9 previous cases with metastases from colorectal cancer have been reported to date, and not much information on urethral metastases from colorectum is available so far.
Case presentation
We report our experience in the diagnosis and the management of the case with urethral metastasis from a sigmoid colon cancer. A 68-year-old man, who underwent laparoscopic sigmoidectomy for sigmoid colon carcinoma four years ago, presented gross hematuria with pain. Urethroscopy identified a papillo-nodular tumor 7 mm in diameter in the bulbar urethra. CT-scan imaging revealed the small mass of bulbous portion of urethra and solitary lung metastasis. Histological examination of the tumor obtained by transurethral resection showed moderately differentiated adenocarcinoma, which was diagnosed as a metastasis of a sigmoid colon carcinoma pathologically by morphological examination. Immunohistochemical analysis of the urethral tumor revealed the positive for cytokertin 20 and CDX2, whereas negative for cytokertin 7. These features were consistent with metastatic adenocarcinoma of the sigmoid colon cancer. As the management of this case with urethral and lung metastasis, 6-cycle of chemotherapy with fluorouracil with leucovorin plus oxaliplatin was administered to the patient, and these metastases were disappeared with no recurrence of disease for 34 months.
Conclusion
Urethral metastasis from colorectal cancer is a very rare occurrence. However, in the presence of urinary symptoms, the possibility of the urethral metastasis should be considered.
doi:10.1186/1471-2482-14-31
PMCID: PMC4037280  PMID: 24884559
Urethral metastasis; Colon cancer; Immunohistochemistry
19.  Urethral obstruction of 6 hours or less causes bacteriuria, bacteremia, and pyelonephritis in mice challenged with "nonuropathogenic" Escherichia coli. 
Infection and Immunity  1993;61(8):3422-3428.
Urethral obstruction may be caused by prostatic hypertrophy, urethral stricture, or encrustation of a urethral-catheter lumen. Bacteriuria often complicates these obstructions. The sequelae include fever, acute pyelonephritis, chronic renal inflammation, and death. We hypothesized that even brief obstruction of the urinary tract containing a nonvirulent bacterium would result in these complications. Mice challenged transurethrally with Escherichia coli FN414, which is rapidly eliminated from normal mice without causing bacteriuria, bacteremia, or renal pathology, were subjected to reversible urethral obstruction by coating the urethral meatus with collodion for 1, 3, or 6 h. The majority of mice obstructed for 1 h demonstrated parenchymal renal inflammation 48 h later. At the end of 3 h of obstruction, 9 of 10 mice were bacteremic; some bacteremias were present at 48 h after removal of the obstruction. At that time, more severe renal inflammation was seen in these mice. As little as 6 h of obstruction resulted not only in the acute changes described above but also in chronic renal inflammation and fibrosis in the majority of animals sacrificed 3 and 6 weeks later. Additional studies demonstrated that urethral obstruction enhanced the uropathogenicity of another nonpathogenic E. coli strain (K-12 strain HB101) and caused more severe renal lesions in mice challenged with E. coli CFT073, isolated from a patient with symptoms of pyelonephritis. These findings demonstrate that brief urethral obstruction may (i) induce organisms which are cleared rapidly from the normal urinary tract to cause bacteriuria, bacteremia, and pyelonephritis and (ii) intensify the renal lesions caused by a uropathogen.
Images
PMCID: PMC281019  PMID: 8335372
20.  High‐risk sexual behaviour in men attending a sexually transmitted infection clinic in Durban, South Africa 
Sexually Transmitted Infections  2007;83(7):530-533.
Objectives
A study of men with genital ulcer disease (GUD) in Durban, South Africa, at the start of the local HIV epidemic in 1988/1989 found that 36% of men with GUD continued with sexual intercourse despite symptoms. The aim of this study was to determine whether this high‐risk behaviour was still prevalent and to enquire about similar risk behaviours with other sexually transmitted infection (STI)‐related problems.
Methods
650 Men attending the main Durban STI clinic with a new complaint were enrolled. A standard questionnaire was administered. Polymerase chain reaction (PCR) tests were performed to diagnose genital herpes from ulcer specimens and gonorrhoea and chlamydia from those with urethral discharge and/or dysuria. Serology tests were performed for HIV, herpes simplex virus type 2 (HSV‐2) and syphilis.
Results
Sex since the start of symptoms was reported by between 33.3% and 43.9% of men with GUD, herpetic ulcers, gonorrhoea and/or chlamydia or dysuria. The incidence of condom use was very low in all groups having sex despite symptoms. In 87 men with genital ulcers confirmed positive for genital herpes by PCR testing, 30 (34.4%) had had sex since the start of symptoms, 28 (93.3%) of whom had had unprotected sex.
Conclusions
There is a high level of risk behaviour in this group of men in whom genital herpes is the most common cause of GUD. This risky sexual behaviour could reflect disinhibition, possibly because so many have already been infected with HSV‐2, lack of education or other unknown factors. Syndromic STI management should be strengthened with intensive health education to promote community awareness of both genital ulceration and genital herpes and their role in facilitating HIV transmission. The low level of condom use indicates that condom promotion programmes still have much to achieve.
doi:10.1136/sti.2007.026716
PMCID: PMC2598658  PMID: 17971375
21.  Effect of local infection and oral contraception on immunoglobulin levels in cervical mucus. 
Infection and Immunity  1975;11(2):215-221.
The concentrations of immunoglobulin A (IgA) and immunoglobulin G (IgG) were estimated in cervical mucus from 115 patients attending a clinic for sexually transmitted diseases. The patients were divided into two groups; those using combined estrogen/progestogen oral contraceptives, and those with presumed normal ovulatory cycles. Gonorrhea, trichomoniasis, candidosis, and herpes genitalis were diagnosed by conventional smear and culture techniques, and the two groups were subdivided according to these diagnoses. Gonorrhea, trichomoniasis, herpetic, and nonspecific cervicitis all caused marked increases in the mean concentrations when compared with a control group of uninfected patients with natural cycles (P = less than 0.01). Patients with candidosis and contacts of men with nonspecific urethritis showed a lesser rise. IgG/IgA ratios lower than that of serum suggested a considerable locally produced contribution of IgA. Oral contraception with the combined pill also caused a significant increase in mean IgA and IgG levels even in the absence of local infection (P = less than 0.01). an increase in the IgG/IgA ratio of this group may indicate that the hormonal effect was manifest through increased serum transudation. IgM was also detected more commonly in patients taking the pill. The marked effect of local disease on immunoglobulin levels in cervical mucus which occurs even in asymptomatic patients emphasizes the importance of screening for infection when studying these secretions.
PMCID: PMC415048  PMID: 163217
22.  Tubal Buccal Mucosa Graft without Anastomosis of the Proximal Urethra for Long Segment Posterior Urethral Defect Repair 
Korean Journal of Urology  2012;53(10):737-740.
A 31-year-old man was referred for further management of a urethral stricture. He was a victim of a traffic accident and his urethral injury was associated with a pelvic bone fracture. He had previously undergone a suprapubic cystostomy only owing to his unstable general condition at another hospital. After 3 months of urethral injury, direct urethral anastomosis was attempted, but the surgery failed. An additional 4 failed internal urethrotomies were performed before the patient visited Chungbuk National University Hospital. Preoperative images revealed complete posterior urethral disruption, and the defect length was 4 cm. We performed a buccal mucosa tubal graft without anastomosis of the proximal urethra for a long segment posterior urethral defect. The Foley catheter was removed 3 weeks after the operation and the patient was able to void successfully. After 8 months, he had normal voiding function without urinary incontinence.
doi:10.4111/kju.2012.53.10.737
PMCID: PMC3490097  PMID: 23136637
Mouth mucosa; Transplants; Urethral stricture
23.  Cell-Seeded Tubularized Scaffolds for Reconstruction of Long Urethral Defects: A Preclinical Study 
European urology  2012;63(3):531-538.
Background
The treatment options for patients requiring repair of a long segment of the urethra are limited by the availability of autologous tissues. We previously reported that acellular collagen-based tubularized constructs seeded with cells are able to repair small urethral defects in a rabbit model.
Objective
We explored the feasibility of engineering clinically relevant long urethras for surgical reconstruction in a canine preclinical model.
Design, setting, and participants
Autologous bladder epithelial and smooth muscle cells from 15 male dogs were grown and seeded onto preconfigured collagen-based tubular matrices (6 cm in length). The perineal urethral segment was removed in 21 male dogs. Urethroplasties were performed with tubularized collagen scaffolds seeded with cells in 15 animals. Tubularized constructs without cells were implanted in six animals. Serial urethrography and three-dimensional computed tomography (CT) scans were performed pre- and postoperatively at 1, 3, 6, and 12 mo. The animals were euthanized at their predetermined time points (three animals at 1 mo, and four at 3, 6, and 12 mo) for analyses.
Outcome measurements and statistical analysis
Statistical analysis of CT imaging and histology was not needed.
Results and limitations
CT urethrograms showed wide-caliber urethras without strictures in animals implanted with cell-seeded matrices. The urethral segments replaced with acellular scaffolds collapsed. Gross examination of the urethral implants seeded with cells showed normal-appearing tissue without evidence of fibrosis. Histologically, an epithelial cell layer surrounded by muscle fiber bundles was observed on the cell-seeded constructs, and cellular organization increased over time. The epithelial and smooth muscle phenotypes were confirmed using antibodies to pancytokeratins AE1/AE3 and smooth muscle–specific desmin. Formation of an epithelial cell layer occurred in the unseeded constructs, but few muscle fibers formed.
Conclusions
Cell-seeded tubularized collagen scaffolds can be used to repair long urethral defects, whereas scaffolds without cells lead to poor tissue development and strictures. This study demonstrates that long tissue-engineered tubularized urethral segments may be used for urethroplasty in patients.
doi:10.1016/j.eururo.2012.07.041
PMCID: PMC3554849  PMID: 22877501
Urethra; Stricture repair; Cell-seeded tubularized urethra reconstruction; Tissue-engineered urethra
24.  A Retrospective Evaluation of Challenges in Urethral Stricture Management in a Tertiary Care Centre of a Poor Resource Community 
Nephro-urology Monthly  2013;5(5):974-977.
Background
Management of urethral stricture has evolved over the years with better understanding of the pathology, advancement in imaging, and introduction of several techniques of urethral reconstruction. In sub-Saharan Africa, advancement in management of urethral stricture may not be comparable with what obtained in most developed nations because of problems like late presentation and persistence of rare complications still reported in recent literature from the region.
Objectives
We set to evaluate the challenges faced by urologists involved in the management of urethral strictures in Osogbo, a poor resource community in south western Nigeria.
Patients and Methods
A retrospective study was performed in the urology unit of Ladoke Akintola University of Technology Teaching Hospital, Osogbo, Nigeria between July 2007 and July 2012. Information was retrieved from patients’ clinical notes and analyzed using statistical package for social sciences (SPSS) version 16.0.
Results
Eighty-four patients were treated during the period of study, their ages ranged between 19 and 89 years with the mean age of 52.3 years. The mean duration of symptoms before presentation was 3 years and 1 month. Inflammation resulting from sexually transmitted infection was the commonest etiology and more than 50% of the patients presented with complications. Sixteen patients (19.1%) received no treatment due to lack of fund. More than 90% were dependent, unemployed or underemployed. Single stage reconstruction by urethral substitution was the commonest form of repair with the restenosis rate of 4.4%.
Conclusions
Prevalent socio-cultural and economic situation in south western Nigeria have added some peculiar challenges to the management of urethral stricture in the region.
doi:10.5812/numonthly.13053
PMCID: PMC3955289  PMID: 24693504
Constriction; Surgical Flaps; Transplants; Inflammation; Fibrosis; Fistula
25.  The outcome of corneal grafting in patients with stromal keratitis of herpetic and non-herpetic origin 
Aim: To evaluate the outcome of corneal grafting in patients with stromal keratitis of herpetic (HSK) and non-herpetic origin, using predefined diagnostic criteria and standardised postoperative therapeutic strategies.
Methods: 384 adult immunocompetent recipients of a corneal graft for herpetic (n = 186) or non-herpetic (n = 198) keratitis were followed up prospectively for up to 5 years.
Results: The herpetic group displayed significantly more corneal vascularisation (p = 0.013), more epithelial defects (p = 0.049), lower corneal sensitivity (p <0.001), more graft rejection episodes (p = 0.002), and required larger grafts (p<0.001). However, the postoperative course of visual acuity, endothelial cell numerical density, and rate of graft failures were similar in both groups. After 5 years, cumulative probability of graft survival in HSK patients (40.85%) was similar to that observed in individuals with non-herpetic keratitis (50.15%; log rank = 0.874; relative risk: 1.04).
Conclusion: Despite a markedly higher preoperative risk profile in herpetic eyes, the functional outcomes of grafts in individuals with keratitis of herpetic or non-herpetic origin were similar. Probably the most important contribution is a consequent close follow up and a therapeutic strategy including systemic prophylaxis of viral recurrence and of graft rejection by well adopted local steroid therapy.
PMCID: PMC1771166  PMID: 12034687
keratitis; herpes simplex virus; corneal transplantation; risk factors

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