Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis

Background  

We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres.     

Antimicrobial resistance associated with the treatment of bacterial vaginosis

OBJECTIVE: This study was undertaken to evaluate antimicrobial susceptibility of vaginal anaerobic bacteria before and after treatment of bacterial vaginosis. STUDY DESIGN: A randomized clinical trial of 119 nonpregnant women with bacterial vaginosis receiving either intravaginal metronidazole for 5 days or clindamycin for 3 days was performed. Women had 1 baseline and 3 follow-up visits at which quantitative vaginal cultures were performed. Anaerobic isolates underwent antimicrobial susceptibility testing. RESULTS: Complete susceptibility data was available on 95 women (47 metronidazole and 48 clindamycin). Of 1059 anaerobic bacterial isolates, less than 1% demonstrated resistance to metronidazole. In contrast, 17% demonstrated baseline clindamycin resistance, and 53% demonstrated resistance to clindamycin after therapy. Women exposed to clindamycin (but not metronidazole) had high frequencies (80%) of clindamycin-resistant anaerobic bacteria that persisted for 90 days after treatment. CONCLUSION: Treatment of bacterial vaginosis with clindamycin is associated with marked evidence of antimicrobial resistance among vaginal anaerobic bacteria. This may increase the vaginal reservoir of macrolide-resistant bacteria.     

Ability of the clinician and patient to predict the outcome of mifepristone and misoprostol medical abortion

We performed this analysis to evaluate the ability of both women and their clinicians to predict pregnancy expulsion after using mifepristone and misoprostol for medical abortion up to 63 days gestation. Women who participated in a multicenter, randomized trial comparing misoprostol 6-8 h vs. 23-25 h after mifepristone attended a follow-up visit approximately 7 days after mifepristone treatment. Each subject was asked if she felt she had expelled the gestational sac. Clinicians also assessed if the sac had been expelled based on the woman's history. Vaginal ultrasonography was then performed to assess the uterine cavity. Of the 1080 women enrolled in the multicenter study, 931 (86.2%) who attended the first follow-up visit by study day 12 and did not have a uterine suction aspiration prior to this visit were included in this analysis. Vaginal ultrasonography at the first follow-up visit demonstrated expulsion in 915 [98.3%, 95% confidence interval (CI): 97.2-99.0] women. Overall, sensitivity, specificity, and positive and negative predictive values for subjects were 96.5%, 31.3%, 98.8% and 13.5%, respectively. When both the clinician and patient felt that the gestational sac had passed (n = 880 [94.5%, 95% CI: 92.9-95.9]), expulsion was confirmed by sonography in 99.1% (95% CI: 98.2-99.6) of cases. Women and clinicians are very accurate at determining expulsion of gestational sac during medical abortion with mifepristone and misoprostol without ultrasonography or a physical examination.     

GSH depletion enhances adenoviral bax-induced apoptosis in lung cancer cells

The utility of dominant acting proapoptotic molecules to induce cell death in cancer cells is being evaluated in preclinical studies and clinical trials. We recently developed a binary adenoviral expression system to enable the efficient gene transfer of Bax and other proapoptotic molecules. Using this system, overexpression of Bax protein in four non-small-cell lung cancer (NSCLC) cell lines, H1299, A549, H226 and H322, was evaluated. The H322 line exhibited significant resistance to Bax-induced cell death compared to the other cell lines. H322 cells had the highest level of glutathione (GSH). GSH levels were significantly decreased following buthionine sulfoximine treatment and this coincided with enhanced apoptosis induction by Ad-Bax in H322 cells. GSH depletion enhanced Bax protein translocation to mitochondrial membranes. These findings suggest that the redox status may be a determinant of Bax-mediated cell death and that manipulation of intracellular thiols may sensitize cells to apoptosis by facilitating Bax insertion into mitochondrial membranes.     

Safety and efficacy evaluations for vaginal and rectal use of BufferGel in the macaque model

BACKGROUND: The nonhuman primate model allows for safety and efficacy testing of topical microbicide products. GOAL: The goal of this study was to evaluate the safety and efficacy of vaginal and rectal applications of BufferGel (ReProtect, Inc.). STUDY DESIGN: The safety of repeated product applications was evaluated by microflora, pH, vaginal colposcopy, and rectal lavage. To test efficacy in preventing chlamydia, infection was documented by culture and nucleic acid amplification tests. RESULTS: Repeated vaginal or rectal applications of BufferGel were not associated with significant changes in microflora. BufferGel use had a transient acidifying effect on vaginal and rectal pH. Colposcopic observations remained relatively normal in all test animals. A slightly increased incidence of epithelial desquamation was noted after rectal product use compared with the control group. BufferGel did not prevent cervical or rectal chlamydial infection. CONCLUSION: BufferGel has an acceptable safety profile after repeated vaginal and rectal use, but does not prevent chlamydial infection in the macaque models.     

Plasma versus serum for detection of herpes simplex virus type 2-specific immunoglobulin G antibodies with a glycoprotein G2-based enzyme immunoassay

To evaluate the consonance between plasma and serum for the detection of herpes simplex virus type 2-specific immunoglobulin G antibodies, we compared results from concurrently obtained plasma and sera in 710 sexually active women by using a glycoprotein G2-based enzyme-linked immunosorbent assay (Focus Technologies, Cypress, Calif.) and found 98.9% agreement between the two specimen types. Plasma appears to be an acceptable matrix for use with this assay.     

Accuracy of serum beta-human chorionic gonadotropin cutoff values at 42 and 49 days' gestation

OBJECTIVE: The accuracy of serum beta-human chorionic gonadotropin levels as cutoff values for estimating gestational age was studied. MATERIAL AND METHODS: A database was created using information from previously performed research studies, which allowed entry of women both less than and greater than 49 days' gestation, involving medical abortion. Serum beta-human chorionic gonadotropin determinations and vaginal ultrasonography were performed in all studies before treatment. A total of 574 women had data available for analysis. A receiver operating characteristic curve was created to evaluate the predictive value of potential beta-human chorionic gonadotropin cutoff values for 42 and 49 days' gestation. RESULTS: Appropriate serum beta-human chorionic gonadotropin cutoff values for 42 and 49 days' gestation were 23,745 mIU/mL (sensitivity, 96%; specificity, 91%; positive predictive value, 68%; negative predictive value, 99%) and 71,160 mIU/mL (sensitivity, 95%; specificity, 62%; positive predictive value, 76%; negative predictive value, 91%), respectively. Under 42 days' gestation, the serum beta-human chorionic gonadotropin-time relationship appears to be linear, with a greater diversity of individual values after 42 days. CONCLUSION: Serum beta-human chorionic gonadotropin values can be used with reasonable accuracy to screen for a gestational age up to 49 days' gestation.     

Neuron-specific expression of therapeutic proteins: evaluation of different cellular promoters in recombinant adenoviral vectors

In order to achieve neuron-restricted expression of antiapoptotic proteins, cellular promoters were investigated for their expression profiles in the context of adenoviral vectors. Both the synapsin 1 gene and the tubulin alpha1 gene promoters were strictly neuron specific in cocultures of primary neurons with their essential feeder cells. The neuron-specific enolase gene promoter exhibited only weak activity in cultured hippocampal neurons and was not neuron specific in preparations of cerebellar granule cells. By attaining virtually 100% transduction efficiency we were able to generate "quasi-transgenic" primary neuron cultures using both differentiated and completely undifferentiated hippocampal neurons. In a functional assay, we used the synapsin promoter to evaluate the effect of Bcl-X(L) overexpression on potassium-withdrawal-induced apoptosis of cerebellar granule neurons. We found nearly complete inhibition of caspase-9 and -3 activation and apoptosis, indicating a major role for mitochondrial pathways in this paradigm of neuronal cell death. The excellent suitability of the synapsin promoter as a strong panneuronal promoter was further demonstrated by its restricted neuronal activity in various brain regions of adult rats in vivo.