Ruth Ellen Jones

Influence of Pelvic Floor Muscle Contraction on the Profile of Vaginal Closure Pressure in Continent and Stress Urinary Incontinent Women

PURPOSEnWe characterized the vaginal pressure profile as a representation of closure forces along the length and circumference of the vaginal wall. Vaginal pressure profile data were used to test the hypothesis that the strength of pelvic floor muscle contractions differs significantly between continent women and women with stress urinary incontinence.nnnMATERIALS AND METHODSnVaginal pressure profile recordings were made in 23 continent subjects and in 10 patients with stress urinary incontinence. The recordings characterized closure forces along the entire length of the vagina and identified differences among the anterior, posterior, left and right sides of the vaginal wall. Using a novel, directionally sensitive vaginal probe we made vaginal pressure profile measurements with the women at rest and during pelvic floor muscle contraction while supine.nnnRESULTSnThe nature of the vaginal pressure profile was characterized in terms of force distribution in the anterior and posterior vaginal walls, which was significantly greater than that on the left and right sides. The continent group had significant greater maximum pressure than the stress urinary incontinence group on the posterior side at rest (mean +/- SE 3.4 +/- 0.3 vs 2.01 +/- 0.36 N/cm(2)) and during pelvic floor muscle contraction (4.18 +/- 0.26 vs 2.25 +/- 0.41 N/cm(2)). The activity pressure difference between the posterior and anterior vaginal walls in the continent group was significantly increased when the pelvic floor muscles contracted vs that at rest (3.29 +/- 0.21 vs 2.45 +/- 0.26 N/cm(2)). However, the change observed in the stress urinary incontinence group was not significant (1.85 +/- 0.38 vs 1.35 +/- 0.27 N/cm(2)).nnnCONCLUSIONSnThe results demonstrate that the voluntary pelvic floor muscles impose significant closure forces along the vaginal wall of continent women but not in women with stress urinary incontinence. The implication of these findings is that extrinsic urethral closure pressure is insufficiently augmented by pelvic floor muscle contraction in women with stress urinary incontinence.

Spatial distribution of vaginal closure pressures of continent and stress urinary incontinent women.

Clinically the strength of the contraction of the female pelvic floor is qualitatively evaluated by vaginal tactile palpation. We therefore developed a probe to enable the quantitative evaluation of the closure pressures along the vagina. Four force sensors mounted on the four orthogonal directions of an intra-vaginal probe were used to measure the vaginal pressure profile (VPP) along the vaginal wall. Clinical experiments on 23 controls and 10 patients with stress urinary incontinence (SUI) were performed using the probe to test the hypothesis that the strength of pelvic floor muscle (PFM) contractions, imposed by voluntary contraction, is related to urinary continence. The results show that VPPs, characterized in terms of pressure distribution on the anterior and posterior vaginal walls, are significantly greater than those in the left and right vaginal walls. When the PFM contracted, the positions of the maximum posterior pressures in continent females and SUI patients were 0.63+/-0.15 cm and 1.19+/-0.2 cm proximal from their peak points of anterior pressure, which are 1.52+/-0.09 cm and 1.69+/-0.13 cm proximal from the introitus of vagina, respectively. The statistical analysis shows that the maximum posterior vaginal pressures of the controls were significantly greater than those of the SUI patients both at rest (continent: 3.4+/-0.3 N cm(-2), SUI: 2.01+/-0.36 N cm(-2), p<0.05) and during PFM contraction (continent: 4.18+/-0.26 N cm(-2), SUI: 2.25+/-0.41 N cm(-2), p<0.01). In addition, the difference between the posterior and anterior vaginal walls is significantly increased when the controls contract the PFM. By contrast, there are no significant differences in the SUI group. The results show that the VPP measured by the prototype probe can be used to quantitatively evaluate the strength of the PFM, which is a clinical index for the diagnosis or assessment of female SUI.

Genetic dissection of clonal lineage relationships with hydroxytamoxifen liposomes

Targeted genetic dissection of tissues to identify precise cell populations has vast biological and therapeutic applications. Here we develop an approach, through thexa0packaging and delivery of 4-hydroxytamoxifen liposomes (LiTMX), that enables localized induction of CreERT2 recombinase in mice. Our method permits precise, in vivo, tissue-specific clonal analysis with both spatial and temporal control. This technology is effective using mice with both specific and ubiquitous Cre drivers in a variety of tissue types, under conditions of homeostasis and post-injury repair, and is highly efficient for lineage tracing and genetic analysis. This methodology is directly and immediately applicable to the developmental biology, stem cell biology and regenerative medicine, and cancer biology fields.Targeted genetic dissection of tissues can be used to identify cell populations and lineages. Here the authors develop 4-hydroxytamoxifen liposomes for the localized induction of CreERT2.

Peritoneal dialysis is feasible as a bridge to combined liver-kidney transplant

Patients with combined liver and kidney failure may remain on dialysis for years while awaiting simultaneous liver-kidney transplantation (SLKT). The role of peritoneal dialysis (PD) in patients with advanced liver and kidney failure awaiting SLKT remains to be defined. We present our single-institution experience with PD in cirrhotics, 3 of whom went on to receive successful SLKT. Patients initiated in our PD program between 2006 and 2016 who had both liver and kidney failure were identified. Medical and dialysis records were reviewed retrospectively. Outcomes included mortality, transplantation status, hospitalizations, need for large-volume paracentesis (LVP), peritonitis rates, PD treatment longevity, and albumin level. Twelve patients with combined liver and kidney failure were treated in our PD program. No patients died and 3 patients received SLKT. Four patients remain listed for transplantation. There was no need for LVP after initiating dialysis. The rate of peritonitis was 0.2 events per patient per year, most commonly due to coagulase-negative Staphylococcus. Our data illustrate that PD is a viable bridging therapy for patients with liver and kidney failure who await SLKT.

Author Correction: Genetic dissection of clonal lineage relationships with hydroxytamoxifen liposomes

In the original version of this Article, the authors inadvertently omitted Elizabeth A. Brett, who contributed to the generation of the histology figures, from the author list.This has now been corrected in both the PDF and HTML versions of the Article.

Mechanoresponsive stem cells acquire neural crest fate in jaw regeneration

During both embryonic development and adult tissue regeneration, changes in chromatin structure driven by master transcription factors lead to stimulus-responsive transcriptional programs. A thorough understanding of how stem cells in the skeleton interpret mechanical stimuli and enact regeneration would shed light on how forces are transduced to the nucleus in regenerative processes. Here we develop a genetically dissectible mouse model of mandibular distraction osteogenesis—which isxa0a process that is used in humans to correct an undersized lower jawxa0that involves surgically separating the jaw bone, whichxa0elicits new bone growth in the gap. We use this model to show that regions of newly formed bone are clonally derived from stem cells that reside in the skeleton. Using chromatin and transcriptional profiling, we show that these stem-cell populations gain activity within the focal adhesion kinase (FAK) signalling pathway, and that inhibiting FAK abolishes new bone formation. Mechanotransduction via FAK in skeletal stem cells during distraction activates a gene-regulatory program and retrotransposons that are normally active in primitive neural crest cells, from which skeletal stem cells arise during development. This reversion to a developmental state underlies the robust tissue growth that facilitates stem-cell-based regeneration of adult skeletal tissue.Reversion of adult skeletal stem cells to a developmental state underlies the growth of new bone during jaw regeneration, in a process that relies on mechanotransduction via the focal adhesion kinase protein.

Renal artery aneurysm associated with Leber hereditary optic neuropathy

Leber hereditary optic neuropathy is an inherited, rare, mitochondrial metabolic disease that leads to progressive vision loss due to the accumulation of reactive oxygen species. The disorder has been associated with microangiopathy and macroangiopathy. We present a novel case of saccular left renal artery aneurysm in a 27-year-old man with known Leber hereditary optic neuropathy. The lesion was asymptomatic and grew from 1.8 to 2.0 cm during the course of 1 year. We successfully performed an endovascular left renal artery aneurysm repair.

Correlation of payor status and pediatric transfer for acute appendicitis

BACKGROUNDnTertiary referral centers provide specialty and critical care for patients presenting to hospitals that lack these resources. There is a notion among tertiary centers that outside hospitals are more likely to transfer uninsured or underinsured patients. We examined funding status of patients transferred to our tertiary pediatric hospital for surgical management of appendicitis, hypothesizing that transferred patients were more likely to have unfavorable coverage.nnnMATERIALS AND METHODSnThe electronic medical record was queried for all cases of laparoscopic appendectomy at our hospital between 2011 and 2015. Insurance was grouped into three categories: commercial, Medicaid/Childrens Health Insurance Plan, or none. Transferred patients were compared to patients who presented directly.nnnRESULTSnA total of 5758 patients underwent laparoscopic appendectomy during the study period, of which 1683 (29.2%) were transfer patients. Transfer patients were more likely to be older, with a median age of 10.5 y versus 9.8 y in nontransferred patients (Pxa0≤xa00.0001), and were more likely to be identified as non-Hispanic (50.0% versus 36.5%; Pxa0≤xa00.0001). Insurance coverage was similar between groups. However, subgroup analysis of the hospitals that most frequently used our transfer services revealed a trend to transfer a higher proportion of Medicaid/Childrens Health Insurance Plan patients.nnnCONCLUSIONSnOverall, pediatric patients transferred for laparoscopic appendectomy had similar insurance coverage to patients admitted directly, but subgroup analysis shows that not all centers follow this trend. Transfer patients were more frequently older and non-Hispanic. This builds upon the existing literature regarding the correlation of funding and transfer practices and highlights the need for additional research in this area.