Reproductive and Developmental Toxicity of N,N-Diethyl-m-toluamide in Rats

N,N-Diethyl-m-toluamide (mDET, DEET) is widely used as a topicalinsect repellent. It is the active ingredient in many consumerformulations, which usually contain 10–25% mDET in analcohol base. More concentrated consumer products are also available,including some that are pure technical grade mDET. Persons livingor employed in mosquito-infested areas may have very high seasonalexposures to mDET. Because contradictory reports had been publishedon the reproductive and developmental toxicity of mDET, a seriesof studies was conducted in male and female Sprague-Dawley rats.All treatments were administered by daily subcutaneous injectionsof undiluted mDET. A dose finding study was done using 12 time-matedfemales per group treated on Gestational Days (GD) 6–15with 0.50, 0.62, 0.78, 0.92, or 1.2 ml mDET /kg/day. No femalessurvived 10 days of mDET dosing with 1.2 ml/kg/day. Deaths occurredin all other groups except the low dose (0.50 ml/kg/ day). Pregnantfemales treated on GD 6–15 with 0 or 0.30 ml/ kg/day wereused for the teratology study. Half of each group was euthanizedon GD 20: the second half was singly housed in nesting boxesand allowed to deliver litters. Live pups were counted and weighedsoon after birth on Postnatal Day (PD) 0 and again on PD 3,9, and 14. Proven fertile males were treated 5 days/week for9 weeks with 0, 0.30, 0.73, 1.15, or 1.80 ml mDET /kg/day fora male dose-finding study. Each group consisted of 20 males.No males survived the 1.80 ml/kg/day. Deaths occurred in allremaining dose groups except the 0.30 ml/kg/ day and controlgroup. Immediately following the final treatment of the maledose study, 11 males were randomly selected from the 0.30 and0.73 ml/kg/day groups. They were cohabited for 7 days with 4females per male during post-treatment Weeks 1 and 2. Half ofthe females were euthanized 12–14 days after the lastday of cohabitation for a dominant lethal study; the remainingfemales were singly housed in nesting boxes and allowed to deliverlitters. Live pups were counted and weighed on PD 0 and 3. Therewas no evidence of reproductive or developmental toxicity inany of these assays, but there were signs of neuro-toxicityin treated adult male and female rats, which may relate to reportsof neurotoxicity in humans heavily exposed to mDET -containinginsect repellents, o 1992 society of Toxicology.     

Use and Performance of Premounted Stents Compared to Nonpremounted Stents in Pediatric and Adult Congenital Cardiac Catheterization

Objectives

We sought to characterize the use, efficacy, and performance characteristics of premounted stents relative to nonpremounted stents when used during congenital cardiac catheterization.

Background

Endovascular stent implantation is an effective means of relieving vascular obstruction in patients with congenital heart disease. However, stent implantation is technically challenging and important complications occur. Premounted stents appear to offer many advantages relative to their nonpremounted counterparts, and it has been suggested that the use of premounted stents is associated with fewer complications. However, translation of these potential benefits into procedural or clinical success has been poorly examined and the data are conflicting.

Methods

All stent placements performed between January 1, 1999 and December 31, 2009 were reviewed. Analysis of technical success, hemodynamic success and complications was performed.

Results

416 stents were placed over the 10 year period. 158 (38%) were premounted. There was no apparent trend in the frequency of use of premounted stents over the study period. Implanted premounted stents were smaller in diameter than nonpremounted stents 4.9 mm +/? 1.8 versus 13.9 mm +/? 3.7, and the site of stent placement differed significantly. Unadjusted and adjusted analysis of technical success with respect to the precision of stent placement, hemodynamic success, and complications showed no difference between premounted and non‐premounted stents.

Conclusions

We found no difference between premounted and nonpremounted stents with respect to procedural and hemodynamic success or complications. Nevertheless, there remain practical advantages to the use of premounted stents that may justify their expanding role in congenital cardiac catheterization. (J Interven Cardiol 2013;26:58–61)

     

CORTICAL RESPONSE TO A TACTILE STIMULUS DURING ATTENTION, MENTAL ARITHMETIC AND FREE ASSOCIATIONS

Attention to a stimulus appears to be associated with amplitude fluctuations in 100-msec or later components of the cortical compound evoked potential (CEP). In this study, changes in amplitude and latency of the CEP to the same tactile stimulus were investigated under three conditions: attention, free associations, and mental arithmetic. In the attention condition Ss were asked to estimate varying time intervals between stimuli on a 2- to 6-sec scale. Ss were 12 pairs of twins. It was found that the amplitudes of two negative electrocortical potentials were greater when Ss were estimating lengths of time intervals between stimuli than during free association or mental arithmetic. Peak latency of the second negative potential was greater in attention than in the other two conditions. Free association CEPs were distinguished by the incidence of a bursts. The results support the hypothesis that attention is associated with certain parameters of the electrocortical response and suggest which aspects of the electrocortical response are most likely to be related to attention.     

An assessment of factors influencing flexibility of human fingernails

A new instrument has been developed and used to determine the effect of various materials on nail flexibility. It repeatedly flexes longitudinal nail sections through 90 degrees and records the number of flexions required to fracture each section. Immersion in water or a phospholipid-water preparation (PLW) greatly increases the flexibility of untreated and lipid extracted nails; immersion in mineral oil does not. Nail flexibility is directly related to the duration of their immersion in water. During water immersion, nail weight increases by 22% of its original weight within 2 h, and then decreases. The rapid increase in nail flexibility during water immersion is related to nail water content. It is possible to prolong the flexibility of previously hydrated nails by the application of PLW or mineral oil. PLW is more effective than water alone in prolonging flexibility of nails extracted with a mixture of acetone, water and acetic acid.     

Fractionated Total Body Irradiation in Bone Marrow Transplantation – An Emphasis on Lung Dosimetry

The use of fractionated total body irradiation is now replacing the large single dose technique originally used in many centres. Twenty-three patients have received this form of therapy prior to marrow transplantation at St. Vincent's Hospital. Doses of 12 to 14 Gray are delivered over 3 to 3 days treating twice daily. Particular emphasis is placed on the amount of radiation received by the lungs and the prescribed dose is related directly to this. The rationale of this technique is discussed, together with the methods of dose calculation, set-up, and incidence of side-effects. Fractionation results in a regime that is very well tolerated with a lower morbidity than that seen with single dose irradiation.     

In Anterior Myocardial Infarction, Frequency Domain is Better than Time Domain Analysis of the Signal-Averaged ECG for Identifying Patients at Risk for Sustained Ventricular Tachycardia

Low amplitude signals at the end of the QRS in patients with prior myocardial infarction (MI) are related to fragmentation of the electrical impulse in ventricular myocardium and are known to correlate with an increased risk of sustained ventricular tachycardia (VT). We hypothesized that in patients with anterior MI (AMI), earlier activation of the damaged anterior wall would cause an earlier fragmentation of the signal-averaged EGG (SAECG) signal, making conventional time domain analysis of late potentials difficult. We performed SAECG in 213 patients (62 with AMI and 58 with inferior MI [IMI]). Fifty-seven had prior sustained VT; 23 with AMI and 24 with IMI. We examined the standard time domain SAECG parameters including the duration of the filtered QRS (40–250 Hz), the duration of the late QRS < 40 μV, and the root mean square amplitude of the last 40 msec of the QRS. We also examined the power law scaling (PLS) in the frequency domain. Receiver operating characteristic curve analysis of a discriminant function demonstrated significant differences for PLS as compared to time domain indices. An important finding was the significance of MI locus in the time domain indices. PLS did not exhibit this dependence. These data suggest that the usual indices are insufficient for identifying AMI patients at risk of VT. PLS, on the other hand, is valuable regardless of MI location.     

CHRONIC TREATMENT WITH FINASTERIDE DAILY DOES NOT AFFECT SPERMATOGENESIS OR SEMEN PRODUCTION IN YOUNG MEN

PURPOSE: Finasteride, an oral type 2, 5alpha-reductase inhibitor, is used in 1 mg. daily doses for the treatment of male pattern hair loss. A dose of 5 mg. finasteride daily reduces ejaculate volume by approximately 25%, and reduces prostate volume by approximately 20% and serum prostate specific antigen (PSA) by approximately 50% in men with benign prostatic hyperplasia. To our knowledge no data exist on the effect of 1 mg. finasteride daily on ejaculate volume or other semen parameters, or on the prostate in young men. Therefore, we studied the potential effect and reversibility of effect of 1 mg. finasteride daily on spermatogenesis, semen production, the prostate and serum PSA in young men. MATERIALS AND METHODS: In this double-blind, placebo controlled multicenter study 181 men 19 to 41 years old were randomized to receive 1 mg. finasteride or placebo for 48 weeks followed by a 60-week off-drug period. Of the 181 men 79 were included in a subset for the collection and analysis of sequential semen samples. RESULTS: There were no significant effects of 1 mg. finasteride on sperm concentration, total sperm per ejaculate, sperm motility or morphology. Ejaculate volume in subjects on finasteride decreased 0.3 ml. (-11%) compared to a decrease of 0.2 ml. (-8%) for placebo, with a median between treatment group difference of -0.03 ml. (1%, 90% confidence interval -10.4 to 13.1, p = 0.915). There were significant but small decreases in prostate volume (-2.6%) and serum PSA (-0.2 ng./ml.) in the finasteride group, which reversed on discontinuation of the drug. CONCLUSIONS: Treatment with 1 mg. finasteride daily for 48 weeks did not affect spermatogenesis or semen production in young men. The effects of 1 mg. finasteride daily on prostate volume and serum PSA in young men without benign prostatic hyperplasia were small and reversible on discontinuation of the drug.     

Influence of Filtering Techniques on the Time-Domain Analysis, Diagnosis, and Clinical Use of Signal-Averaged Electrocardiogram

In order to investigate the effect of different filtering techniques on the time-domain analysis of signal-averaged electrocardiogram (SAECG), recordings of 1,192 subjects were analyzed using Butterworth and Del Mar filters, both set at 40–250 Hz high and low pass frequencies. The recordings were taken from six clinically defined groups: (a) survivors of acute myocardial infarction (n = 553); (b) patients with sustained symptomatic postinfarction ventricular tachycardia (n = 89); (c) patients with hyperthropic cardiomyopathy (n = 219); (d) patients with dilated cardiomyopathy (n = 76); (e) direct relatives of patients with dilated cardiomyopathy (n = 170); and (f) normal healthy volunteers (n = 85). The study investigated differences between the SAECG results reported with both filters in three individual aspects: (l) numerical values of individual time-domain SAECG variables; (2) differences in SAECG findings of patients with postinfarction ventricular tachycardia and pair matched patients with uncomplicated follow-up after acute infarction; and (3) the power of SAECG findings to predict high risk of arrhythmic complication (sudden death and/or sustained ventricular tachycardia) among survivors of acute myocardial infarction. Compared with the Butterworth filter, the Del Mar filter led to a systematic difference of + 8% in total QRS duration, was equally powerful in distinguishing between the pair matched patients with and without postinfarction ventricular tachycardia, and was statistically significantly more powerful in identifying those survivors of acute infarction who were at high risk of arrhythmic complications. The study concludes that the use of different filters may produce discordant results of SAECG analysis. Normal and abnormal values for various types of SAEGG recording and analysis have to be established individually for different equipment and different software settings. These optimal cut-offs of SAEGG variables should also take into account the clinical characteristics of patient groups.