Female genital tuberculosis in light of newer laboratory tests: A narrative review.

Female genital tract tuberculosis (FGTB) is a chronic disease with varied presentation. The diagnosis of FGTB for early institution of treatment remains a clinical challenge. Its laboratory diagnosis is difficult because of paucibacillary nature of the condition and limitation of available diagnostic tests. In view of the intricate problems in diagnosis of FGTB, physicians tend to over treat with empirical anti-tuberculosis drugs. Apart from concerns of drug toxicity, this may be a contributing factor in the increasing incidence of multidrug-resistant TB reported in India. The main goal for advances in TB diagnostics is to reduce delay in diagnosis and treatment. In addition, there should be reduced complexity, improving robustness, and improving accuracy of the laboratory test for diagnosis of Female genital tuberculosis. OBJECTIVE: This narrative review is written with the following objectives. 1) To get a comprehensive overview as well as recent advances in diagnostic test used in the detection of FGTB. 2) To understand the limitations as well as advantages of these laboratory diagnostic test. 3) To provide clinical guidance regarding the detection in susceptible women. METHOD: The literature search was performed using electronic database of Pubmed, Medline, Embase and Google Scholar. Grey literature search was also done. Studies published in English were included. Following keywords were used for search - Tuberculosis, extra pulmonary tuberculosis, female genital tuberculosis, diagnosis of female genital tract tuberculosis. The personal knowledge and experience of authors in the field, helped in archiving the relevant articles. RESULT: Studies suggest that though culture is an invaluable contributor in the diagnosis of FGTB, molecular tests like PCR, LAMP, Xpert MTB/RIF and line probe assays have shown potential and are now being explored to strengthen the diagnostic algorithm of FGTB. CONCLUSION: The use of algorithm approach with combination of both rapid culture and newer molecular techniques will facilitate the accurate and timely diagnosis of FGTB.

Effect of chronic pretreatment with 17ß-estradiol and/or progesterone on the nociceptive response to uterine cervical distension in a rat model.

It is widely known that visceral pain is more prevalent in women than in men, and this phenomenon is interpreted as a consequence of the gonadal hormone modulation of pain perception and transduction. Uterine cervical distension might cause obstetric and gynecologic pain with clinical relevance to visceral pain. In this study, we focused on the roles of 17ß-estradiol and progesterone in visceral nociception with the use of a rat model of uterine cervical distension. Female ovariectomized rats were injected with 17ß-estradiol (E2) or progesterone (P4) for 21 days, after which visceral pain-induced spinal c-fos expression and visceromotor reflex changes were compared between ovariectomized and hormone-substituted groups. We found that uterine cervical distension induced a drastic increase in spinal c-fos expression and visceromotor reflex activity, and ovariectomy inhibited the increase in c-fos expression induced by visceral pain; this inhibition was reversed by estrogen but not progesterone replacement. This study demonstrates that estrogen is involved in uterine cervical nociception, while progesterone plays less of a significant role.

HDR syndrome in a Colombian woman with a genital tract malformation: first case report in Latin America / Síndrome HDR en una mujer colombiana con una malformación genitourinaria: primer reporte de caso en Latinoamérica

ABSTRACT Objectives Hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome, also known as Barakat syndrome, is an autosomal dominant transmission hereditary disease with a wide range of penetrance and expressivity. Haploinsufficiency of the GATA3 two finger zinc transcription factor is believed to be its cause. This is the first time this orphan disease is reported in Latin America, so the publishing of this report is expected to raise awareness on these types of syndrome, that are usually underdiagnosed in our region, which in turn causes an increase in the years lost to disability (YLDs) rates, as well as higher costs to be assumed by public health systems. Methods A 36-year-old Colombian woman diagnosed with parathyroid gland agenesis was referred from the Endocrinology Service to the Outpatient Service. According to her medical record, in the past she had developed hypocalcaemia, left renal agenesis, hypoparathyroidism, bicornate uterus and sensorineural hearing loss. Through a genetic analysis a pathological mutation on the short arm of the GATA 3 gen (c.404dupC, p Ala136 GlyfsTER 167) was confirmed, which led to a HDR syndrome diagnosis. Discussion This case proves that there is a possibility that mutations described in other continents may be developed by individuals from our region. Regardless of ethnicity, Barakat syndrome should be considered as a possible diagnosis in patients presenting the typical triad that has been described for this condition, since there could be underdiagnosis of this disease in Latin-America due to the lack of knowledge on this condition in said region, and that genetic counseling in these patients is of great importance for the implications of the syndrome in future generations.(AU)

RESUMEN Objetivos El síndrome de hipoparatiroidismo, sordera neurosensorial y displasia renal (HDR) también llamado síndrome de Barakat, es una enfermedad hereditaria de transmisión autosómica dominante con amplia penetrancia y expresividad genética. El síndrome es causado por la haploinsuficiencia del factor de transcripción de dedos de Zinc GATA3. Esta es la primera vez que esta enfermedad huérfana es reportada en latinoamerica, y buscamos generar consciencia de la presencia de estas enfermedades, las cuales usualmente son infradiagnósticadas en nuestro medio y llevan a un aumento de años perdidos por discapacidad y costos para el sistema de salud pública. Métodos Una mujer colombiana de 36 años ingresó a consulta externa de genética referida por el servicio de endocrinología por una agenesia de paratiroides. La paciente tenía antecedentes de hipocalcemia, agenesia renal izquierda, hipoparatiroidismo, sordera neurosensorial y útero bicorneo. Se realizó un análisis genético que confirmo una mutación patológica en el brazo corto del gen GATA3 (c.404dupC, p Ala136 GlyfsTER 167) diagnóstica del síndrome de Barakat. Discusión Este caso demuestra la posibilidad de existencia de mutaciones descritas en otros continentes en nuestra población. Sin importar la etnia, el síndrome de Barakat debe ser estudiado en pacientes que presenten la triada típica, ya que podría existir un infra diagnóstico de la enfermedad secundario al desconocimiento de la misma en Latinoamérica y teniendo en cuenta la importancia que tiene la consejería genética en estos pacientes por las implicaciones de la enfermedad en futuras generaciones.(AU)

Vaginal Delivery After Dührssen Incisions in a Patient With Bladder Exstrophy and Uterine Prolapse.

BACKGROUND: Bladder exstrophy is a rare congenital anomaly affecting the lower abdominal wall, pelvis, and genitourinary structures. Pregnant women with bladder exstrophy present a unique challenge to the obstetrician. CASE: The patient is a 35-year old pregnant woman with bladder exstrophy, an extensive surgical history, and uterine prolapse with an abnormal, rubbery consistency to her cervix. Prenatally, she was counseled on the potential use of Dührssen incisions to facilitate vaginal delivery. Labor was induced at 36 4/7 weeks of gestation after her pregnancy was complicated by recurrent pyelonephritis. Vaginal delivery was achieved 8 minutes after the creation of Dührssen incisions. CONCLUSION: The care of pregnant women with bladder exstrophy requires multidisciplinary management and careful delivery planning. Successful vaginal delivery can be attained in these patients.

The reporting of study and population characteristics in degenerative cervical myelopathy: A systematic review.

OBJECT: Degenerative cervical myelopathy [DCM] is a disabling and increasingly prevalent condition. Variable reporting in interventional trials of study design and sample characteristics limits the interpretation of pooled outcomes. This is pertinent in DCM where baseline characteristics are known to influence outcome. The present study aims to assess the reporting of the study design and baseline characteristics in DCM as the premise for the development of a standardised reporting set. METHODS: A systematic review of MEDLINE and EMBASE databases, registered with PROSPERO (CRD42015025497) was conducted in accordance with PRISMA guidelines. Full text articles in English, with >50 patients (prospective) or >200 patients (retrospective), reporting outcomes of DCM were deemed to be eligible. RESULTS: A total of 108 studies involving 23,876 patients, conducted world-wide, were identified. 33 (31%) specified a clear primary objective. Study populations often included radiculopathy (51, 47%) but excluded patients who had undergone previous surgery (42, 39%). Diagnositic criteria for myelopathy were often uncertain; MRI assessment was specified in only 67 (62%) of studies. Patient comorbidities were referenced by 37 (34%) studies. Symptom duration was reported by 46 (43%) studies. Multivariate analysis was used to control for baseline characteristics in 33 (31%) of studies. CONCLUSIONS: The reporting of study design and sample characteristics is variable. The development of a consensus minimum dataset for (CODE-DCM) will facilitate future research synthesis in the future.

[First year experience using arabin cervical pessary with intravaginal micronized progesterone for the prevention of preterm birth in patients with mid-trimester short cervix].

BACKGROUND: Arabin cervical pessary is a silicone ring pessary for the prevention of preterm birth (PTB] for pregnant women at risk with second trimester short uterine cervix. Progesterone supplementation has been found to prevent PTB. OBJECTIVE: To review our first year of experience using Arabin cervical pessary with intravaginal micronized progesterone in the prevention PTB. METHODS: The study included patients (pt) with singleton and twin pregnancies at 16-30 weeks with uterine cervical length < or = 25 mm treated with Arabin cervical pessary and intravaginal progesterone over one year from September 2011 to September 2012. Progesterone treatment was continued until 34 weeks and pessary was extracted at 36 weeks or in cases of preterm labor, bleeding or other medical indications. RESULTS: The study group included 43 patients, 31 (72.1%) singleton and 12 (27.9%) twins. The average week at admission was 25+2 weeks [w] [SD +/- 3.05], and the average cervical length at admission was 13.5 mm (SD +/- 5.0). A total of 11 patients had previous PTB; in 2 patients the pessary was placed after cerclage failure. The average week of delivery was 35 + 5 weeks SD +/- 3.2 (singleton 36 + w SD +/- 2.6, twins 33 + 4 SD +/- 4.1, p = 0.05); the average time between pessary insertion to delivery 72.1 days SD +/- 26.2 (singleton 76.3 SD +/- 22.9 twins 60.2 SD +/- 28.9 p = 0.02), in 23 patients (53.5%) the pessary was extracted at > or = 36 + 6w, 5 patients 111.6%) delivered < or = 32w (2 singleton, 3 twins, p = 0.08) and 18 patients (41.8%) reported increased vaginal discharge. CONCLUSION: The use of cervical pessary in conjunction with intravaginal progesterone is safe and feasible. Patients with twin pregnancies had a significantly higher rate of preterm birth compared to singleton pregnancies. Further research is needed to assess device efficacy.

Isolated hydatid cyst of uterine cervix: A case report.

Hydatid disease is an endemic infection which can affect any organ, mainly the liver and lungs. Peritoneal echinococcosis is usually known to occur secondary to hepatic hydatid cyst rupture into the peritoneal cavity. An isolated cyst in the pelvic cavity is considered as primary only when there are no other hydatid cysts. Herein, we report an isolated pelvic-cervical hydatid cyst which presented without any involvement of the other abdominal organs or lungs. Our patient, a 27-year-old woman with the primary complaints of dyspareunia and chronic pelvic pain, had thin-walled large cystic mass originating from the cervix, diagnosed by ultrasonography. She underwent surgery with the most likely initial diagnosis of exophytic fibroid with cystic degeneration. Gynecologists should be aware of the possibility of isolated primary hydatid cyst of the pelvic cavity and should consider this condition in the differential diagnosis of cystic pelvic masses, especially in areas where the disease is endemic.

[Embryo transfer in case of stenosed and/or forbidding cervix]. / Transfert embryonnaire en cas de col sténosé et/ou infranchissable.

A cervical stenosis can follow an infection, a conisation or a trachelectomy and lead to a cervical infertility. In in vitro fertilization (IVF), embryo transfers are difficult in case of a cervical stenosis and specific care is required. Treatments try to restore an adequate cervical patency. Repeated cervical dilatations can represent a solution. In case of inefficiency, a new cervicoisthmic opening has to be created with surgery. Perpetuity of the result is obtained thanks to post surgical dilatations or thanks to implementation of an intracervical catheter till complete cicatrization. In case of failure of canalization of the stenosed isthmic os, alternative treatments can be proposed. Intraperitoneal insemination in the poutch of Douglas is interesting when tubes are patent and when semen quality is sufficient. On the contrary, transmyometrial embryo transfer and gametes or zygotes intrafallopian transfer represent an ultimate therapeutic option.

Oncogenic human papillomavirus DNA loads in human immunodeficiency virus-positive women with high-grade cervical lesions are strongly elevated.

Human papillomavirus (HPV) DNA loads of six oncogenic HPV types were measured by real-time PCR in cervical scrapes of human immunodeficiency virus (HIV)-infected and uninfected women. In both groups, HPV loads increased with the grade of cervical disease. HIV infection did not affect HPV loads in low-grade lesions but was associated with significantly higher HPV loads in severe dysplasia; highest loads were found in advanced HIV disease. Our data reflect the aggressive course of HPV infection in HIV-positive women.

Human papillomavirus type 16-specific T cell responses and their association with recurrence of cervical disease following treatment.

Human papillomavirus type 16 (HPV-16) L1- and E7-specific T cell responses were measured in 58 women with abnormal cervical cytology in a prospective study. On recruitment, patients responded most frequently and with the highest numbers of responding cells to the L1 region aa 311-345 and this response was significantly associated with the presence of cervical disease (P=0.041). Responses to the L1 peptide aa 281-295 were significantly higher in patients with CIN III than in those with HPV/CIN I or CIN II lesions (P=0.027). The E7 region aa 70-98 was the most immunogenic in patients with squamous intraepithelial lesions of the cervix (SIL) but the responses detected were not significantly higher than in patients without SIL. Following treatment, the T cell response profiles of patient groups did not change significantly. However, on analysis of the responses of individual patients with and without recurrent disease on follow-up, significant differences were found. Recurrence of disease was associated with T cell responses to the E7 region aa 70-98 at the patient's first clinic visit (P=0.017). Recurrence of disease was also accompanied by an increase in the total number of L1-specific short-term T cell lines (STLs) at follow-up, whereas absence of disease was accompanied by a decrease in L1-specific STLs. The data also suggested a possible link between E7 70-98-specific responses and acquisition of disease by patients who were previously disease-free. Further studies are warranted to determine whether this response could be useful as a marker of recurrent disease in some patients.

Incidence, prevalence, and clearance of type-specific human papillomavirus infections: The Young Women's Health Study.

The natural history of type-specific human papillomavirus (HPV) infections was examined in a cohort of 331 women aged 18-35 years who self-referred for routine gynecological care. Participants underwent a gynecological examination at baseline and at approximately 4 and approximately 10 months after baseline. Cervical samples were collected for HPV testing and genotyping at each visit, as was information on reproductive, sexual, and medical histories. The rate of new HPV infections was 2.9% per month; the highest rates were observed for HPV types 16, 39, 84, and 51. Among women who tested negative for HPV at baseline, the cumulative probability of acquiring an oncogenic HPV strain during a 12-month follow-up period was 0.32, compared with 0.18 for nononcogenic strains. Women who had had >/=1 new male sex partner in the recent past were significantly more likely to acquire a new HPV infection (relative hazard, 2.39; 95% confidence interval, 1.20-4.76). The median time to clearance of infection was significantly longer for oncogenic strains (9.8 months) than for nononcogenic strains (4.3 months).

Mitotic activity and apoptosis in endocervical glandular lesions.

To evaluate the significance of mitotic activity and apoptosis in the differential diagnosis of endocervical glandular lesions, we examined the frequency of mitoses and apoptosis in 89 endocervical glandular lesions from 78 patients, which consisted of benign reactive changes (7 cases), lobular or diffuse laminar endocervical glandular hyperplasia (4), microglandular hyperplasia (3), tunnel clusters (7), nabothian cysts (2), mesonephric remnants (3), tubal metaplasia (3), endocervical glandular dysplasias (including atypical tubal metaplasia) (EGD) (7), adenocarcinoma in situ (AIS) (31), microinvasive adenocarcinoma (7), frankly invasive adenocarcinoma (12), and minimal deviation adenocarcinoma (3). Mitotic index (MI; mitotic figures per 1000 cells) was significantly higher in AIS, microinvasive adenocarcinoma, and frankly invasive adenocarcinoma than any other lesions examined. Microinvasive adenocarcinoma showed the highest MI. Apoptosis was detected consistently and frequently in AIS, microinvasive adenocarcinoma, and frankly invasive adenocarcinoma. AIS showed the highest apoptotic index (AI; apoptoses per 1000 cells). Frequent apoptotic bodies and mitotic figures are a common feature of endocervical glandular malignancies (except for minimal deviation adenocarcinoma) and are an important feature that can facilitate their differentiation from benign and borderline lesions. High MI in microinvasive adenocarcinoma might aid the distinction of microinvasive adenocarcinoma from AIS. Although both MI and AI of EGD were between those of benign reactive changes and of AIS, MI and AI alone are not sufficient to differentiate EGD from benign reactive changes. MI and AI are not helpful in the differential diagnosis between minimal deviation adenocarcinoma and its benign mimics.

Prevalence and prediction of sexually transmitted diseases among sex workers in Cameroon.

The aim of the study was to determine the prevalence of sexually transmitted diseases (STDs), describe the frequency of genitourinary symptoms and signs, and to assess the accuracy of clinical diagnoses of STD in a cohort of Cameroonian sex workers. Physical examinations were conducted on 1233 sex workers in Yaoundé and Douala, Cameroon. Symptoms experienced within the 14 days prior to examination were collected. Women were tested for gonorrhoea, chlamydia infection, and trichomoniasis. Doctors' clinical impressions were compared with laboratory tests. Prevalence of cervical infection and trichomoniasis was 20%. A high percentage of abnormal signs and symptoms was found in this cohort. Clinical diagnosis for cervicitis and trichomoniasis had low sensitivities (<50%) while specificity remained high (>65%). In conclusion STDs are common among sex workers in Cameroon. Clinical diagnosis was not an accurate predictor of infection at the individual level in this population at risk of STD.

PIP: The prevalence of sexually transmitted diseases (STDs) and the frequency of genitourinary symptoms and signs were assessed in 1233 female prostitutes aged 18-45 years, of mean age 26, in Yaounde and Douala. Researchers recorded the physical signs and symptoms experienced by the study subjects within 14 days prior to the physical examination provided as part of the study. The women were tested for gonorrhea, chlamydia infection, and trichomoniasis, with doctors' clinical impressions compared to laboratory test findings. 20% had cervicitis; gonorrhea (11%), chlamydia (12%), or both (3%). 20% had a positive wet mount test for trichomoniasis; 10 subjects were diagnosed with gonorrhea, chlamydia, and trichomoniasis; 65.1% reported abnormal vaginal discharge; and 44.7% reported pelvic pain. Clinical diagnosis for cervicitis and trichomoniasis in this study had sensitivities of less than 50% and specificities of greater than 65%. STDs are therefore common among prostitutes in Cameroon and clinical diagnosis was not an accurate predictor of infection at the individual level.

[Role of cervical modifications in threatened premature labor]. / Rôle des modifications du col utérin dans la menace d'accouchement prématuré.

Uterine cervical modifications play a central role in preterm labor and are one of the main indicators for the clinical diagnosis of this syndrome. Modifications of the cervix are either isolated events "cervical incompetence" or associated with cervicovaginal infection, which is an important etiological factor. Furthermore, the extent of cervical modifications in preterm labor is probably related to the prognosis of preterm delivery. Certain developments in the treatment of preterm pregnancy have focused on the uterine cervix (e.g. cervical cerclage, treatment of cervicovaginal infections) and such strategies may facilitate the prevention of preterm delivery. The information currently available emphasizes an independent role for the uterine cervix in preterm labor. As a consequence, it should be realised that even though there is a direct association between cervical modifications and uterine contractions, management of preterm labour must not be directed exclusively at the control of uterine contractions and tocolysis.