Pelvic-Floor Rehabilitation, Part 2 : Pelvic-Floor Reeducation With Interferential Currents and Exercise in the Treatment of Genuine Stress Incontinence in Postpartum Women : A Cohort Study

Background and Purpose. This descriptive cohort study investigated a physical therapy program of pelvic-floor neuromuscular electrostimulation (NMES) combined with exercises, with the aim of developing a simple, inexpensive, and conservative treatment for postpartum genuine stress incontinence (GSI). Subjects. Eight female subjects with urodynamically established GSI persisting more than 3 months after delivery participated in the study. The subjects ranged in age from 24 to 37 years (X̅=32, SD=4.2). Methods. This was a descriptive multiple-subject cohort study. Each subject received a total of nine treatment sessions during 3 consecutive weeks, consisting of two 15-minute sessions of NMES followed by a 15-minute pelvic-floor muscle exercise program. Patients also practiced daily pelvic-floor exercises during the 3-week treatment period. The treatment intervention was measured using three separate variables. Maximum muscle contractions (pretraining, during training, and posttraining) were measured indirectly as pressure, using perineometry. Urine loss pretraining and posttraining was measured by means of a Pad test. Self-reported frequency of incontinence was recorded daily throughout the period of the study, using a diary. Data were analyzed using a one-way repeated measures analysis of variance (ANOVA), a Wilcoxon signed-ranks test, and a Friedman two-way ANOVA by ranks. Results. The results indicated that maximum pressure generated by pelvic-floor contractions was greater and both the quantity of urine loss and the frequency of incontinence were lower following the implementation of the physical therapy program. Five subjects became continent, and three others improved. A follow-up survey 1 year later confirmed the consistency of these results. Conclusion and Discussion. The results suggest that the proposed physical therapy program may influence postpartum GSI. Further studies are needed to validate this simple, inexpensive, and conservative physical therapy protocol.

Pelvic-Floor Rehabilitation, Part 1 : Comparison of Two Surface Electrode Placements During Stimulation of the Pelvic-Floor Musculature in Women Who Are Continent Using Bipolar Interferential Currents

Background and Purpose. Electrical stimulation of the pelvic floor is used as an adjunct in the conservative treatment of urinary incontinence. No consensus exists, however, regarding electrode placements for optimal stimulation of the pelvic-floor musculature. The purpose of this study was to compare two different bipolar electrode placements, one suggested by Laycock and Green (L2) the other by Dumoulin (D2), during electrical stimulation with interferential currents of the pelvic-floor musculature in continent women, using a two-group crossover design. Subjects. Ten continent female volunteers, ranging in age from 20 to 39 years (X̅=27.3, SD=5.6), were randomly assigned to one of two study groups. Methods. Each study group received neuromuscular electrical stimulation (NMES) of the pelvic-floor musculature using both electrode placements, the order of application being reversed for each group. Force of contraction was measured as pressure (in centimeters of water [cm H2O]) exerted on a vaginal pressure probe attached to a manometer. Data were analyzed using a two-way, mixed-model analysis of variance. Results. No difference in pressure was observed between the two electrode placements. Differences in current amplitude were observed, with the D2 electrode placement requiring less current amplitude to produce a maximum recorded pressure on the manometer. Subjective assessment by the subjects revealed a preference for the D2 electrode placement (7 of 10 subjects). Conclusion and Discussion. The lower current amplitudes required with the D2 placement to obtain recordings comparable to those obtained with the L2 technique suggest a more comfortable stimulation of the pelvic-floor muscles. The lower current amplitudes required also suggest that greater increases in pressure might be obtained with the D2 placement by increasing the current amplitude while remaining within the comfort threshold. These results will help to define treatment guidelines for a planned clinical study investigating the effects of NMES and exercise in the treatment of urinary stress incontinence in women postpartum.

Le CpG et le poly(I:C) agissent en synergie avec le trastuzumab contre le cancer du sein HER2+

Chez la souris, la thérapie anti-HER2 est dépendante de la présence de cellules T CD8+IFN-γ+ et des réponses IFN de type I. Ces IFN sont induits par les TLRs suite à la reconnaissance de signaux de danger, appelés PAMPs et DAMPs. Les TLR-3 et TLR-9 sont tous deux de bons inducteurs d’IFN de type I et sont également capable d’agir en synergie afin d’augmenter les niveaux d’IFN-γ, de TNF-α et d’IL-12. Notre hypothèse fut que la stimulation de ces deux TLRs mènerait à l’amélioration de l’activité anti-tumorale du trastuzumab via le recrutement et l’activation des cellules immunitaires. Nos buts furent de confirmer le potentiel thérapeutique de la combinaison de l’anticorps anti-HER2, de l’agoniste de TLR-3, le poly(I:C), et de l’agoniste de TLR-9, le CpG ODN. Des études in vivo et in vitro nous ont permis de découvrir une synergie entre ces agents qui résulte en une cytotoxicité ciblée plus efficace. De plus, cette thérapie s’avéra efficace chez des modèles CD8-dépendants et CD8-indépendents. Les souris purent rejeter leur tumeur et demeurer sains plusieurs semaines après l’arrêt des injections. Ces souris étaient également protégées lors d’un challenge, soulignant ainsi la présence d’une immunité mémoire. Nous avons aussi découvert que l’administration combine de trastuzumab des deux agonistes de TLRs mène à des réponses systémiques. Des études de déplétion confirmèrent que les cellules T CD8+ sont cruciales pour la protection à long terme des animaux, mais que les pDC sont moins impliquées que ce que l’on pourrait croire. Leur absence n’a que modestement affecté les effets de notre thérapie. À l’opposé, les cellules NK sont d’importants médiateurs des effets thérapeutiques. Des expériences d’ADCC ont révélé que le CpG ODN et poly(I:C) ont tous deux la capacité d’améliorer les fonctions des cellules NK, mais que la stimulation simultanée des TLR-3 et TLR-9 permet de maximiser les effets bénéfiques du trastuzumab. De la même manière, l’addition de CpG ODN et de poly(I:C) aux anticorps anti-HER2 a permis d’augmenter les réponses pro-inflammatoires, plus spécifiquement l’IFN-γ, le TNF-α, l’IP-10 et l’IL-12.