The predictive value of basal follicle stimulating and growth hormone levels as determined by immunofluorometry during assisted reproduction

Purpose Our purpose was (a) to investigate relationships of baseline endocrine serum levels with selected assisted reproduction (AR) parameters and (b) to evaluate the clinical applicability of an immunofluorometric assay (IFMA) as an alternative to a radioimmunoassay (RIA).Methods Basal endocrine values (analyzed by RIA—rFSH, rLH, and rE₂; analyzed by IFMA—fFSH, fLH, and fGH) were determined for female patients (n = 142) preceding ovarian stimulation for AR.Results Specific AR parameters correlated significantly with RIA- and IFMA-determined FSH levels, although IFMA correlations consistently exceeds that of RIA. Cutoff values of fFSH 11.68 IU/L or rFSH 15.0 IU/L indicated a poor response. The high-basal fFSH group was older (34 vs 31 years; P = 0.0334) and yielded fewer oocytes (2.9 vs 4.6 oocytes; P = 0.0018) than the low-basal fFSH group (<11.68 IU/L). Lower cumulative embryo scores and conception rates were also associated with the high-fFSH group, compared to the low-fFSH group.Conclusions This study confirms the negative impact of elevated basal FSH levels on AR. Basal LH, GH, and E₂ levels are, in comparison to baseline FSH levels, unsuitable indices for estimating ovarian responsiveness. IFMA can be regarded as an alternative to RIA in both clinical and research laboratories.     

Primary Bladder Neck Obstruction: Urodynamic Findings and Treatment Results in 36 Men

Purpose

We reviewed the urodynamic findings and treatment outcomes of a large series of men with primary bladder neck obstruction.

Materials and Methods

A retrospective review was done of the presenting symptoms and urodynamic findings of 36 men with primary bladder neck obstruction. Outcomes after treatment with alpha-blockers, transurethral incision of the bladder neck and prostate, or no long-term therapy were determined by chart review and patient survey in the majority of cases.

Results

Mean age of the men was 41 years. Patients had significant lower urinary tract symptoms, decreased peak urinary flow rates, elevated post-void residual, markedly elevated peak voiding pressures and poor funneling of the bladder neck during voiding. Although most patients initially chose alpha-blocker therapy, only 30 percent of those beginning alpha-blockers continued them long term, usually due to inadequate symptomatic improvement. A total of 18 men underwent transurethral incision, which resulted in significant improvements in symptom scores, peak urinary flow rates, post-void residual and peak voiding pressures. Patients reported a mean 87 percent overall improvement in symptoms after transurethral incision.

Conclusions

Video urodynamics facilitate diagnosis of primary bladder neck obstruction. Transurethral incision is the most effective therapy for primary bladder neck obstruction.     

Effect of recombinant interleukin-2 pretreatment on oral and intravenous digoxin pharmacokinetics and P-glycoprotein activity in mice.

P-glycoprotein (P-gp) is an ATP-dependent efflux membrane transporter involved in many drug pharmacokinetics in humans. Decreasing its expression could enhance the bioavailability of substrates as digoxin. We have recently found that human recombinant interleukin-2 (rIL2) in vivo decreases P-gp expression in intestine and brain of mice and modifies oral digoxin pharmacokinetics. The aim of the study was to evaluate the involvement of bioavailability in the rIL2 pretreatment effect on digoxin pharmacokinetics by comparing oral and i.v. digoxin pharmacokinetics before and after rIL2 pretreatment (10 microg/kg). We also tried to show the possible effect of a low rIL2 dose (1 microg/kg) pretreatment on oral digoxin pharmacokinetics. First, adult Swiss mice received a single oral or i.v. dose of digoxin (0.03 mg/kg). Two weeks later, the same animals were treated by rIL2 i.p. twice a day (10 microg/kg) for 4 days and received digoxin again at day 5. As well, another group received oral digoxin (0.03 mg/kg) with a 1 microg/kg rIL2 pretreatment. Blood was collected after digoxin administration with and without rIL2 pretreatment. Digoxin pharmacokinetics were described by a one-compartment model. The 10 microg/kg rIL2 pretreatment did not modify i.v. digoxin pharmacokinetics, whereas oral digoxin pharmacokinetics were significantly modified by the 10 microg/kg rIL2 pretreatment and not by the 1 microg/kg rIL2 pretreatment. The decrease of P-gp activity, caused by rIL2 (10 microg/kg), increased digoxin bioavailability. An increase in exposure and intracellular level of drugs is expected from rIL2 pretreatment.     

Influence of the punch diameter and curvature on the yield pressure of MCC-compacts during Heckel analysis.

The volume reduction behaviour of powders has been quantified by means of the 'in-die' yield pressure (YP) using Heckel analysis. However, because different YPs are reported for the same material, the experimental conditions influencing this material-constant were investigated. Silicified microcrystalline cellulose was compressed into flat-faced and convex tablets using a compaction simulator instrumented with load and displacement transducers. During compression, upper and lower punch force and displacement data were recorded and corrected for punch deformation. A symmetrical triangle wave compression profile was used and the instantaneous punch velocity was kept constant (5mm/s). Individual tablet height and weight were used for Heckel analysis. The influence of the 'effective compression pressure' (P(EFF)) (ranging from 10 to 350 MPa), punch diameter (PD) (4, 9.5 and 12 mm) and filling depth (FD) (4.5, 7.5 and 10.5mm) on YP was statistically evaluated using Response Surface Modelling software. A quadratic surface response equation, describing the relationship between P(EFF), PD, FD and YP, was proposed for concave (Adj R(2): 0.8424; S.D.: 14.60 MPa) and flat-faced (Adj R(2): 0.8409; S.D.: 4.49 MPa) punches. YP and tensile strength were mainly determined by P(EFF), irrespective of punch curvature. FD and PD had only a minor influence on the YP, although more pronounced for the concave punches. The method used resulted in reproducible P(EFF) and tensile strength values and the flat-faced tablets showed less weight variation. Flat-faced punches are preferred over punches with a concave surface when investigating the volume reduction behaviour of a powder by means of Heckel analysis and the experimental parameters should be reported.     

Spatial and temporal variability of contaminants of emerging concern in a drinking water source

The spatial–temporal behaviour of contaminants of emerging concern (CECs) are not well-documented in drinking water sources, including in Quebec, Canada. In this study, a set of seven contaminants, which are more frequently reported in water sources, were monitored from May 2016 to August 2017 at ten locations within an urbanized watershed (lakes and rivers) in Quebec, Canada. Samples were collected between a wastewater plant discharge (upstream) and the intake of a drinking water plant (downstream). The results showed that three (acetaminophen, salicylic acid, caffeine) out of seven CECs were consistently detected at a range of up to a few hundred ng L⁻¹ at all sampling stations throughout the sampling period with a detection frequency between 51% and 94%. Upstream of two wastewater plant discharge locations, six CECs were measured above the detection limit compared to other locations where only three CECs (acetaminophen, salicylic acid, caffeine) were detected. Most of the CEC concentrations were higher (a few ng L⁻¹) during late winter in comparison with the summer, in both years 2016 and 2017. The results highlight that the wastewater effluents and septic system effluents are significant sources of CECs that are released into the surface water. Moreover, the results help to identify the spatio-temporal patterns, which is a crucial element to understand the fate of CECs in water sources submitted to extreme weather conditions during the year. This research also provides baseline data for CEC occurrence at different points across lakes, rivers, and tributaries which will be useful for future ecotoxicological studies.

The spatial–temporal behaviour of contaminants of emerging concern (CECs) are not well-documented in drinking water sources, including in Quebec, Canada.     

Feasibility of a randomized controlled trial testing nifedipine vs. placebo for the treatment of preterm labor

AIMS: Nifedipine is believed to be a superior tocolytic agent on the basis of efficacy and side-effect profile, but was never prospectively evaluated in a placebo-controlled randomized clinical trial (RCT). In our study, we sought to identify limitations in participation for a would-be RCT comparing nifedipine to placebo. METHODS: A prospective feasibility study was conducted at Ste-Justine Hospital, a tertiary care center, on women between 24 and 34 weeks' gestation, presenting to the labor and delivery room with obstetrical complaints. Patient information was collected and would-be participants were identified on the basis of pre-established clinical and ultrasound criteria as well as on willingness to participate, as determined by the study research nurse. RESULTS: During a 6-month period, 483 women presenting with signs and symptoms of preterm labor (PTL) were eligible for further evaluation. A total of 321 (66.5%) women were excluded for obstetrical and medical reasons whereas 125 (25.9%) did not meet strict inclusion criteria (cervical length <25 mm or positive fetal fibronectin). When using strict criteria, only 37 women (7.6%) were found to be eligible for study participation. Subject willingness to participate as assessed by the research nurse was 50%. CONCLUSIONS: If adhering to strict inclusion/exclusion criteria, the feasibility of an appropriately sampled RCT testing tocolytic therapy against a placebo would require a large concerted multicenter effort to meet sample size demands.