Factors associated with nucleic acids related to human immunodeficiency virus type 1 in cervico-vaginal secretions.

OBJECTIVE: To assess HIV-related nucleic acids in cervico-vaginal secretions and the factors associated with them. DESIGN: Observational study. SETTING: Department of Obstetrics and Gynaecology, University of Pavia, Italy. POPULATION: HIV-positive patients attending a cytology service. METHODS: Paired blood and cervico-vaginal lavage samples were obtained from 122 known HIV-seropositive patients during periodic visits for cytologic screening for lower genital tract neoplasia. Vaginal specimens for the diagnosis of bacterial vaginosis, trichomonas vaginalis and candida infection were also obtained. HIV-1-RNA in plasma, proviral HIV-1-DNA, cell associated and cell-free HIV-1 RNA in cervico-vaginal secretions were quantitatively evaluated by competitive polymerase chain reaction (c-PCR) and reverse transcriptase PCR (cRT-PCR). MAIN OUTCOME MEASURE: Prevalences of HIV related nucleic acids in cervico-vaginal secretions and their univariate and multivariate associations with clinical variables. RESULTS: Proviral HIV-1 DNA, cell-associated and cell-free HIV-1 RNA were detected in 50% (61/122), 37.7% (46/122) and 32.8% (40/122) of the patients, respectively. In logistic regression analysis, the presence of HIV-1 RNA in blood was the factor which correlated best with the detection of HIV-1 DNA (OR = 5.48, 95% CI = 2.28-13.20), cell-associated (OR = 4.85; 95% CI = 1.89-12.45) and cell-free HIV-1 RNA (OR = 4.63, 95% CI = 1.74-12.33) in cervico-vaginal samples. However, between 20% and to 35% of patients who tested negative for blood HIV-1 RNA were positive for either HIV-1 DNA or HIV-1 RNA detection in cervico-vaginal lavages. Bacterial vaginosis was associated with an increased prevalence of cell-associated (OR = 3.58, 95% CI = 1.22-10.54) and cell-free HIV-1 RNA (OR = 2.94, 95% CI = 1.0-8.7) detection in cervico-vaginal secretions. Additional factors associated with increased prevalence of HIV-1 RNA detection were advanced stage of HIV disease and vulvovaginal candidiasis. CONCLUSIONS: Although the presence of HIV-1 RNA in blood is the factor which correlates best with the detection of HIV-related nucleic acids in cervico-vaginal secretions, the shedding of HIV in the genital tract can occur in 20-30% of non-viremic subjects. Bacterial vaginosis and candida infection could have a facilitating role in local HIV viral replication and shedding.

Human immunodeficiency virus type 1-related nucleic acids and papillomavirus DNA in cervicovaginal secretions of immunodeficiency virus-infected women.

OBJECTIVE: To evaluate simultaneous human immunodeficiency virus (HIV)-related nucleic acids and human papillomavirus (HPV)-DNA in cervicovaginal secretions of HIV-seropositive women. METHODS: We collected 47 paired blood and cervicovaginal lavage samples from 124 known HIV-1-seropositive women. Proviral HIV-1 DNA, cell-associated, and cell-free HIV-1 RNA in cervicovaginal secretions were quantitatively evaluated by competitive polymerase chain reaction (PCR) and reverse transcription PCR. Polymerase chain reaction and subsequent restriction fragment length polymorphism analysis of PCR products were used to detect HPV types 6, 11, 16, 18, 31, 33, 35, and 56. RESULTS: Proviral HIV-1 DNA, cell-associated, and cell-free HIV-1 RNA were detected in 52.4% (65 of 124), 38.7% (48 of 124), and 33.9% (42 of 124) of lavage samples, respectively. Human papillomavirus-DNA in cervicovaginal secretions was detected in 64% (79 of 124) of participants. The rate of detection of HPV types of intermediate to high oncogenic risk was higher in HIV-positive women who tested positive for cell-associated (odds ratio [OR] 3.57, 95% confidence interval [CI] 1.17, 11.12) or cell-free (OR 4.63, 95% CI 1.42, 15.51) HIV-1 RNA in cervicovaginal secretions than their counterparts who tested negative. Logistic regression analysis showed that the association between HPV infection and the detection of HIV-1 RNA in cervicovaginal secretions persisted after adjustment for potential confounders such as CD4+ cell counts, HIV-1 RNA in plasma, use of antiretroviral drugs, vaginal infection, and regular condom use. In univariable and multivariable analysis, HPV-DNA detection was associated with amounts of cell-free and cell-associated HIV-1 RNA in cervicovaginal secretions (chi(2) for trend 10.35, and 9.84, P =.001 and.002, respectively). CONCLUSIONS: The rate of HPV detection in the genital tract of HIV-1-seropositive women is associated with the amount of cell-associated and cell-free HIV-1 RNA present in cervicovaginal secretions. The association does not appear to be attributable entirely to the effect of HIV-related immunodepression.

Viral excretion in cervicovaginal secretions of HIV-1-infected women receiving antiretroviral therapy.

A longitudinal study was conducted to evaluate the viral shedding present in cervicovaginal secretions of HIV-1-seropositive women receiving antiretroviral therapy. A total of 128 paired cervicovaginal and blood samples was obtained from 37 women during a median follow-up period of 21 months. A sensitive, competitive, polymerase chain reaction and a reverse transcription polymerase chain reaction were used for the simultaneous quantitation of HIV-1 proviral DNA and RNA in cervicovaginal cells and cell-free RNA in cervicovaginal secretions, as well as HIV-1 RNA in peripheral blood. The cumulative probability of detecting proviral DNA in genital secretions was significantly higher over time in women with detectable viremia than in women in whom HIV-1 RNA was persistently undetectable in plasma (< 50 copies/ml) (P = 0.028 by log-rank test). The presence and amount of proviral DNA, cell-associated RNA and cell-free RNA in the cervicovaginal secretions were positively correlated with the presence of detectable viremia or the number of HIV-1 RNA copies in plasma (Spearman rank correlation, 0.290, 0.279, and 0.305, respectively; all P < 0.01), but no correlation was found with the CD4+ cell count. In addition, vaginal infections were positively correlated with the detection of proviral DNA in cervicovaginal secretions (odds ratio, 2.60; 95% confidence interval, 1.07-5.70). However, the positive correlation between the presence and amount of HIV in cervicovaginal secretions and the viral load in plasma provides no assurance that HIV shedding does not occur in the genital tract of women with undetectable HIV-RNA in plasma.

Effect of antibiotic use on the prevalence of symptomatic vulvovaginal candidiasis.

OBJECTIVE: The purpose of the study was to evaluate the influence of antibiotic use on the prevalence of symptomatic vulvovaginal candidiasis. STUDY DESIGN: This is a case-control study of 684 women with symptomatic vulvovaginal candidiasis who were enrolled at a vaginitis clinic and 901 control subjects who attended a cytologic screening service. RESULTS: The prevalence of antibiotic use in the month preceding the visit was 19.3% (132/684) among patients with Candida infection compared with 11.9% (107/901) among control subjects (P <.001). After adjustment by logistic regression for potential confounders (age, marital status, and contraceptive method used), the odds ratio for vulvovaginal candidiasis among patients who reported antibiotic use in the month preceding the visit was 1. 75 (95% confidence interval 1.33 to 2.32). No differences in risk were found by type of antibiotic used. The likelihood of vulvovaginal candidiasis was directly related to the duration of antibiotic use and was higher in patients who had a history of repeated episodes of Candida vaginal infection. CONCLUSIONS: Antibiotic use is a short-term risk factor for symptomatic vulvovaginal candidiasis, either as a first episode or in the form of recurrence. Increasing duration of antibiotic use is directly related with an increased prevalence of Candida vaginal infection.

Obstetric risk factors for periventricular leukomalacia among preterm infants.

OBJECTIVE: To evaluate the obstetric antecedents of cystic periventricular leukomalacia and transient echodense periventricular lesions among preterm infants. DESIGN: A cohort study of preterm singleton infants born between 25 and 33 weeks gestation. SETTING: Pavia, Italy. POPULATION: Three hundred and forty-nine infants admitted to a Division of Neonatal Intensive Care who were screened for periventricular leukomalacia. METHOD: The obstetric factors in infants with either cystic periventricular leukomalacia or transient echodense periventricular lesions were compared to those in infants with negative cranial ultrasonographic findings. Stepwise multiple logistic regression analysis was used to evaluate the association between risk factors and outcomes adjusting for confounders. RESULTS: The prevalence of cystic periventricular leukomalacia and transient echodense lesions was 5.7% (20/349) and 14% (49/349), respectively. The main risk factors for cystic leukomalacia were first trimester haemorrhage (OR 4.49; 95% CI 1.63-12.39), maternal urinary tract infection on admission (OR 5.71; 95% CI 1.91-17.07), and neonatal acidosis (pH < 7.2) at birth (OR 5.97; 95% CI 1.93-18.52). Meconium-stained amniotic fluid (OR 3.95; 95% CI 1.42-10.98) and long term (> 72 hours) ritodrine tocolysis (OR 2.54; 95% CI 1.28-5.05) were associated with an increased risk of echodense lesions. The likelihood of overall leukomalacia (cystic plus echodense periventricular lesions) was increased among cases with meconium-stained amniotic fluid (OR 4.06; 95% CI 1.65-10.0), long-term ritodrine tocolysis (OR 2.56; 95% CI 1.38-4.72), maternal infection (OR 1.73; 95% CI 1.0-3.0), and acidosis at birth (OR 1.98; 95% CI 1.0-3.98). CONCLUSIONS: This study confirms that maternal infection, acidosis at birth, and meconium-stained amniotic fluid increase the risk of periventricular leukomalacia in preterm infants. Long-term ritodrine use seems to increase the risk for transient echodense lesions.

Adequacy of screening cervical cytology among human immunodeficiency virus-seropositive women.

OBJECTIVE: To evaluate the adequacy of cytology in detecting cervical intraepithelial neoplasia (CIN) among human immunodeficiency virus (HIV)-seropositive women compared to controls. METHODS: A cross-sectional study was carried out evaluating 241 HIV-seropositive women and 991 controls (404 HIV seronegative and 587 of unknown HIV status) at risk for CIN attending a vaginitis clinic. All patients had a Pap smear and a standard colposcopic examination of the lower genital tract. Cervical biopsies were taken as indicated by colposcopy. Cytology and histology slides were read by a cytopathologist blinded to patients' serostatus. False-negative cytologic cases were reviewed by three independent cytopathologists to estimate sampling and screening error rates. Sensitivity, specificity, and false-negative rate of cytologic smears were compared between HIV seropositives and controls. We estimated the sampling and screening error rates among cases with false-negative cytology. RESULTS: Among seropositives, the sensitivity, specificity, and the false-negative smear rate for CIN were 73.4% (47/64), 97.1% (134/138), and 26.6% (17/64), respectively. The corresponding figures in controls were 83.8% (83/99), 99.04% (825/833), and 16.2% (16/99), respectively, and did not differ significantly from those of seropositives. The negative predictive value of cytology was lower among seropositives (134/151) than in controls (825/841, chi2 = 34.8, P < .001). The agreement between cytologic readings and combined colposcopy and histology was stronger among controls (kappa = 0.789, 95% CI 0.723 to 0.856) than among seropositives (kappa = 0. 593, 95% CI 0.475 to 0.712). Three independent cytopathologists were unable to detect atypical cells in 52.9% (9/17) of false-negative smears taken from seropositive women as opposed to 37.5% (6/16) of controls. CONCLUSIONS: The sensitivity, specificity, and false negative rate of screening cytology for CIN among HIV seropositive women are comparable with those in the general population. Since almost 50% of false-negative results could be attributed to sampling errors, more frequent cytological screening may prove to be beneficial to this high-risk group.

Preeclampsia, preterm delivery and infant cerebral palsy.

OBJECTIVE: To evaluate the association between preeclampsia and cerebral palsy among preterm infants. STUDY DESIGN: A cohort study of 345 singleton preterm (24 to 33 weeks gestation) infants delivered at an institution where no mothers received magnesium sulphate. We investigated the relationship of preeclampsia to the development of infant cerebral palsy (spastic quadriplegia, hemiplegia or diplegia) at two years' corrected age. Potential confounders were controlled for by politomous logistic regression analysis. RESULTS: The prevalence of cerebral palsy in surviving infants from normotensive and preeclamptic pregnancies was 13.4% (38/284) and 3.3% (2/61), respectively (P=0.026 by Fisher exact test). After control for potential confounders (gestational age, infant gender, birthweight standard deviation score, mode of delivery), the likelihood of infant cerebral palsy was reduced by preeclampsia (odds ratio 0.16, 95% confidence interval=0.04-0.74 for infants from preeclamptic versus normotensive pregnancies being palsied). CONCLUSION: Among preterm infants, the protective effect of preeclampsia against cerebral palsy is manifest in the absence of magnesium sulphate utilization.

The relationship of bacterial vaginosis, Candida and Trichomonas infection to symptomatic vaginitis in postmenopausal women attending a vaginitis clinic.

OBJECTIVE: To estimate the prevalence of bacterial vaginosis, Candida albicans, and Trichomonas vaginalis infections in a population of postmenopausal women with symptoms of vaginitis seen at a vaginitis clinic either as self-referred or clinician referred patients. METHODS: A cross-sectional study of 148 postmenopausal women (cases) and 1564 controls of reproductive age attending a vaginitis clinic. C. albicans and T. vaginalis infections were diagnosed by culture techniques. Bacterial vaginosis was diagnosed on the basis of clinical findings. RESULTS: Fifty-six (37.8%) postmenopausal women and 834 (53.3%) controls were diagnosed with T. vaginalis or C. albicans infection, or bacterial vaginosis, or mixed infection (odds ratio (OR) 0.53, 95% confidence interval (CI) 0.37-0.75). C. albicans and T. vaginalis infection were diagnosed in 34.1% (534/1564) and 1.92% (30/1564) of women of childbearing age and in 13.5% (20/148) and 10.8% of postmenopausal women, respectively. (P < 0.05 for both comparisons). The prevalence of bacterial vaginosis was similar between the two groups (14/148 in postmenopausal patients and 210/1564 in controls of reproductive age; P = 0.22). CONCLUSIONS: Among postmenopausal women attending a vaginitis clinic, a defined diagnosis of bacterial vaginosis, C. albicans or T. vaginalis infection can be made in about one third of such patients. Concerning the two thirds of symptomatic women lacking such a microbiologic diagnosis, alternative causes (e.g., estrogen deficiency, nonanaerobic bacterial infections, local irritants or allergenes, and dermatologic conditions) need to be considered.

Cervical intraepithelial neoplasia in pregnant intravenous drug users infected with human immunodeficiency virus type 1.

OBJECTIVE: The purpose of this study was to evaluate the frequency and natural history of cervical intraepithelial neoplasia (CIN) during pregnancy in past or current intravenous drug users infected with human immunodeficiency virus type 1 (HIV-1). STUDY DESIGN: We prospectively evaluated 48 pregnant HIV-1 seropositive patients and 38 HIV seronegative controls. All the subjects were current or past intravenous drug users. Follow-up visits were carried out each trimester of pregnancy and 8-12 weeks post-partum with Papanicolau smears, colposcopic examinations and, when necessary, colposcopically directed cervical biopsies. RESULTS: Thirteen of 48 HIV-seropositive women (27.1%) and three of 38 HIV-seronegative controls (7.9%) (P = 0.027 by Fisher exact test) had biopsy-proven CIN at the beginning of pregnancy. High-grade CIN was detected in 10 cases (20.8%) and in two (5.3%) controls (P = 0.058 by Fisher exact test). None of the cervical squamous intraepithelial lesions progressed throughout pregnancy, in both cases and controls. Post-partum cold-knife cervical conization was performed on seven patients with CIN III and examination of the cone biopsy specimens demonstrated persistence of CIN III. CONCLUSIONS: HIV-infected intravenous drug users are at high risk of CIN during pregnancy, thus requiring adequate screening programs. Our preliminary data suggest that the progression rate of CIN during gestation is low in this high-risk group.

A new approach to the use of the Krukenberg procedure in unilateral wrist amputations. An original functional-cosmetic prosthesis.

A new therapeutic approach based on the Krukenberg procedure for patients with wrist amputations, together with a functional-cosmetic prosthesis, is described. The indications for this surgery are modified since the operation was originally designed for patients with bilateral wrist amputations or for the blind patient with a unilateral or bilateral amputation. This new approach is based on personal observations and studies of the socioeconomic condition of many amputated patients in Venezuela who reject the use of a conventional prosthesis or orthesis.