Retrospective Study of Long-term Surgical Outcomes in Patients Who had a Vaginal Hysterectomy in Conjunction with Pelvic Organ Prolapse Surgery.

INTRODUCTION: Data on long-term outcomes and subjective patient symptom improvement following primary native tissue pelvic organ prolapse repair is limited. Our primary aim was to evaluate the long-term prolapse recurrence and retreatment rates of women who have undergone native tissue prolapse repair. Our secondary aim was to evaluate subjective patient improvement in pelvic floor symptoms and quality of life 7 to 10 years after surgery. METHODS: This retrospective cohort study included patients who had undergone primary prolapse repair surgery including a hysterectomy and native tissue repair by a single surgeon at a tertiary pelvic floor center from 2009 to 2013. The Pelvic Floor Distress Inventory was distributed to subjects before and 7 to 10 years after surgery and preand post-operative survey results were compared. Subjects were asked if they had symptom recurrence and if they required retreatment. RESULTS: One hundred twelve of the 204 distributed surveys were returned, yielding a 54.9% response rate. 8.6% of subjects reported prolapse symptom recurrence. 1.9% of subjects were retreated with a pessary. No subjects required additional prolapse repair surgery. 77.1% of subjects had improved PFDI-20 scores following surgery with an average improvement of 46.21 points. Statistically significant score improvements were also observed on PFDI-20 subsections. CONCLUSIONS: Primary pelvic organ prolapse repair utilizing native tissue results in low recurrence and retreatment rates. Patients can expect long-term clinical improvement in pelvic floor disorders and quality of life following prolapse surgery. Definitions of surgical success should be based on subjective patient symptoms and quality of life measures.

Electric scooters: a quick way to get to the emergency department?

Introduction Electric scooters (e-scooters) are rife but are yet to be legalised in the UK. The aim of this paper was to investigate whether there had been an increase in the number of e-scooter injuries referred to the oral and maxillofacial surgery (OMFS) service at our unit. We present here what is, to our knowledge, the largest dataset regarding e-scooter-related injuries in the UK.Method A double cohort study in which details of patients sustaining e-scooter-related injuries that were referred to the OMFS department were collected, prospectively, for a 16-week period in 2020 (investigation period). This was compared with data collected, retrospectively, from the emergency department (ED) referral database for the same date range in 2019 (control period).Results In the investigation period, 12/649 referrals to OMFS from the ED were for e-scooter-related injuries. There were eight male patients and four female patients with a mean age of 35 years (interquartile range 24-48). Of these, only one patient was wearing a helmet and 8/12 had consumed alcohol. Head and neck injuries sustained included avulsed teeth, mandibular and midface fractures, skull fractures, facial lacerations and cervical spine injuries. One patient died as a result of their injuries. During the control period, 2/997 ED referrals to OMFS were for e-scooter-related injuries (12/649 versus 2/997; Fisher's exact test p <0.001).Conclusion There was a significant rise in e-scooter-related injuries seen at our major trauma unit compared with 2019. We recommend that e-scooters are subject to at least the same requirements in safety equipment and sobriety as bicycles and that their top speed is limited to 12.5 mph. We hope that these measures will allow the benefits of this technology to be enjoyed while reducing associated morbidity and mortality.

Dually targeted bioinspired nanovesicle delays advanced prostate cancer tumour growth in vivo.

Prostate cancer (PC) is second-leading cancer in men, with limited treatment options available for men with advanced and metastatic PC. Prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) have been exploited as therapeutic targets in PC due to their upregulation in the advanced stages of the disease. To date, several PSA- and PSMA-activatable prodrugs have been developed to reduce the systemic toxicity of existing chemotherapeutics. Bioinspired nanovesicles have been exploited in drug delivery, offering prolonged drug blood circulation and higher tumour accumulation. For the first time, this study describes the engineering of dually targeted PSA/PSMA nanovesicles for advanced PC. PSMA-targeted bioinspired hybrids were prepared by hydrating a lipid film with anti-PSMA-U937 cell membranes and DOX-PSA prodrug, followed by extrusion. The bioinspired hybrids were characterised using dynamic light scattering, transmission electron microscopy, Dot blot, flow cytometry and Western blot. Cellular binding and toxicity studies in PC cancer cell lines were carried out using flow cytometry, confocal microscopy, and resazurin assay. Finally, tumour targeting and therapeutic efficacy studies were performed in solid and metastatic C4-2B-tumor-bearing mice. Interestingly, our PSMA-targeted hybrids demonstrated high cell uptake in PSMA-expressing cells with significant accumulation in solid and metastatic C4-2B tumour tissues following intravenous administration. More promisingly, our dually targeted PSA/PSMA hybrid significantly slowed down the C4-2B tumour growth in vivo, compared to free DOX-PSA and non-targeted PSA-hybrid. Our PSA/PSMA bioinspired hybrid could offer a highly selective treatment for advanced PC with lower side effects. STATEMENT OF SIGNIFICANCE: This study investigates a new approach to treat prostate cancer using dually targeted bioinspired nanovesicle . Our bioinspired vesicles are made mainly of a human blood cell membrane with a ligand recognising a specific marker (PSMA) on the surface of the prostate cancer cells. The present work describes the successful loading of a doxorubicin prodrug linked to a PSA- activatable peptide into these targeted bioinspired nanovesicle , where the active PSA enzyme presents in these cells converts the drug to its active form. Our dually targeted PSA/PSMA hybrid vesicles has successfully improved site-specific prodrug delivery to tackle advanced prostate cancer, offering a novel and effective prostate cancer treatment.

PD1 blockade potentiates the therapeutic efficacy of photothermally-activated and MRI-guided low temperature-sensitive magnetoliposomes.

This study investigates the effect of PD1 blockade on the therapeutic efficacy of novel doxorubicin-loaded temperature-sensitive liposomes. Herein, we report photothermally-activated, low temperature-sensitive magnetoliposomes (mLTSL) for efficient drug delivery and magnetic resonance imaging (MRI). The mLTSL were prepared by embedding small nitrodopamine palmitate (NDPM)-coated iron oxide nanoparticles (IO NPs) in the lipid bilayer of low temperature-sensitive liposomes (LTSL), using lipid film hydration and extrusion. Doxorubicin (DOX)-loaded mLTSL were characterized using dynamic light scattering, differential scanning calorimetry, electron microscopy, spectrofluorimetry, and atomic absorption spectroscopy. Photothermal experiments using 808 nm laser irradiation were conducted. In vitro photothermal DOX release studies and cytotoxicity was assessed using flow cytometry and resazurin viability assay, respectively. In vivo DOX release and tumor accumulation of mLTSL(DOX) were assessed using fluorescence and MR imaging, respectively. Finally, the therapeutic efficacy of PD1 blockade in combination with photothermally-activated mLTSL(DOX) in CT26-tumor model was evaluated by monitoring tumor growth, cytokine release and immune cell infiltration in the tumor tissue. Interestingly, efficient photothermal heating was obtained by varying the IO NPs content and the laser power, where on-demand burst DOX release was achievable in vitro and in vivo. Moreover, our mLTSL exhibited promising MR imaging properties with high transverse r2 relaxivity (333 mM-1 s-1), resulting in superior MR imaging in vivo. Furthermore, mLTSL(DOX) therapeutic efficacy was potentiated in combination with anti-PD1 mAb, resulting in a significant reduction in CT26 tumor growth via immune cell activation. Our study highlights the potential of combining PD1 blockade with mLTSL(DOX), where the latter could facilitate chemo/photothermal therapy and MRI-guided drug delivery.

Developing an Advanced Alternative Payment Model for Stress Urinary Incontinence.

ABSTRACT: Historically, our health care system has been based on a fee-for-service model, which has resulted in high-cost and fragmented care. The Center for Medicare & Medicaid Services is moving toward a paradigm in which health care providers are incentivized to provide cost-effective, coordinated, value-based care in an effort to control costs and ensure high-quality care for all patients. In 2015, the Medicare Access and Children's Health Insurance Program Reauthorization Act repealed the Sustainable Growth Rate and the fee-for-service model, replacing them with a 2-track system: Merit-based Incentive Payment System and the advanced Alternative Payment Model (aAPM) system. In 2016, the American Urogynecologic Society Payment Reform Committee was created and tasked with developing aAPMs for pelvic floor disorders. The purpose of this article is to describe the stress urinary incontinence aAPM framework, the data selected and associated data plan, and some of the challenges considered and encountered during the aAPM development.

Fixation Method and Subsequent Revision Rates for Elective Primary Hip Arthroplasty in People Aged 70 Years and Older: Analysis of National Administrative Data Sets by the UK Getting It Right First Time Program.

BACKGROUND: We aimed to understand the role of fixation method in predicting subsequent revision rates in people aged 70 years and older undergoing elective primary total hip arthroplasty (THA) within the UK National Health Service (NHS). METHODS: Data on elective primary THAs conducted in people aged 70 years and older between April 1, 2012, and March 31, 2018, and subsequent revisions conducted up to March 31, 2019, were extracted from the Hospital Episodes Statistics database for all NHS procedures in England. A flexible parametric competing risks model was used to identify the role of fixation method in predicting revision and adjust for age, sex, frailty, year of surgery, and all-cause mortality. RESULTS: Data were available for 190,656 procedures. Crude revision rates at 1-7 years follow-up in those who had cemented, hybrid/reverse hybrid, and uncemented fixation were 1.8%, 1.8%, and 2.3%, respectively. There was a high level of variation between NHS trusts in the proportionate use of fixation method. The differences in the hazard of revision between uncemented and cemented fixation (hazard ratio, 1.238 [95% confidence interval, 1.148-1.336]) and hybrid/reverse hybrid fixation (hazard ratio, 1.184 [95% confidence interval, 1.082-1.297]) were both significant. In secondary analysis, there was evidence that revision rates in trusts where uncemented fixation predominated were not significantly lower for uncemented fixation compared to all other fixation methods. CONCLUSIONS: Revision rates were significantly higher for elective primary THA in people aged 70 years and older who have uncemented fixation, compared to those who had cemented and hybrid/reverse hybrid fixation.

Naked Liquid Marbles: A Robust Three-Dimensional Low-Volume Cell-Culturing System.

Three-dimensional (3D) multicellular structures allow cells to behave and interact with each other in a manner that mimics the in vivo environment. In recent years, many 3D cell culture methods have been developed with the goal of producing the most in vivo-like structures possible. Whilst strongly preferable to  conventional cell culture, these approaches are often poorly reproducible, time-consuming, expensive, and labor-intensive and require specialized equipment. Here, we describe a novel 3D culture platform, which we have termed the naked liquid marble (NLM). Cells are cultured in a liquid drop (the NLM) in superhydrophobic-coated plates, which causes the cells to naturally form 3D structures. Inside the NLMs, cells are free to interact with each other, forming multiple 3D spheroids that are uniform in size and shape in less than 24 h. We showed that this system is highly reproducible, suitable for cell coculture, compound screening, and also compatible with laboratory automation systems. The low cost of production, small volume of each NLM, and production via automated liquid handling make this 3D cell-culturing system particularly suitable for high-throughput screening assays such as drug testing as well as numerous other cell-based research applications.

Effect of Electronic Video Education on Patient's Self-Assessed Knowledge About Obesity and Pelvic Floor Disorders: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to study the effect of electronic video education on patient's self-assessed perception of knowledge about pelvic floor disorders in relation to obesity in a prospective randomized controlled trial. METHODS: From June to July 2015, women with a body mass index of 25 kg/m or higher seeking care at a single urogynecology center were recruited and randomized into either a standard visit with an 8-minute video (group A) or a standard visit control (group B). Randomization was performed with computer-generated number blocks of 4. Allocation sequence was concealed from the caregiver, in sequentially numbered, opaque, and sealed envelopes. Immediately after their visit, patients answered a series of 3 questionnaires, which were statistically analyzed using unpaired t tests, Wilcoxon rank sum and analysis of variance tests, presented as mean and standard deviation. Primary outcome was a difference in self-assessed perception of knowledge questionnaire scores. Secondary outcome was a difference in motivation to lose weight. RESULTS: Forty-eight women enrolled, and 40 completed all questionnaires, 20 in each group. Representation in both groups was demographically similar. The mean (SD) answers for the postvisit survey measuring participant's self-assessed perception of knowledge was 3.9 (0.8) for group A and 3.5 (1.1) for group B (P = 0.002). Ninety percent of women in group A reported motivation to lose weight, compared with 75% in group B (P = 0.4). CONCLUSIONS: Participants who received electronic video education scored significantly higher on self-assessed perception of knowledge questionnaire about pelvic floor disorders in relation to obesity. The video did not increase motivation to lose weight.

Current Issues with Hysterectomy.

Hysterectomy is one of the most common gynecologic surgeries. Early adoption of surgical advancements in hysterectomies has raised concerns over safety, quality, and costs. The risk of potential leiomyosarcoma in women undergoing minimally invasive hysterectomy led the US Food and Drug Administration to discourage the use of electronic power morcellator. Minimally invasive hysterectomies have increased substantially despite lack of data supporting its use over other forms of hysterectomy and increased costs. Health care reform is incentivizing providers to improve quality, improve safety, and decrease costs through standardized outcomes and process measures.

Effective treatment of dyssynergic defecation using sacral neuromodulation in a patient with cerebral palsy.

BACKGROUND: Dyssynergic defecation is a complex bowel problem that leads to chronic constipation and abdominal pain. Management is often challenging owing to the incoordination of multiple pelvic floor muscles involved in normal defecation. CASE: We report a case of dyssynergic defecatory dysfunction in a patient with cerebral palsy treated with sacral neuromodulation. At presentation, Sitz marker study and magnetic resonance defecography showed evidence of chronic functional constipation. Anorectal manometry, rectal anal inhibitory reflex, and rectal sensation study showed intact reflex and decreased first sensation of lower canal at 50 mL. After stage 2 of InterStim implant placement, bowel habits improved to once- to twice-daily soft solid bowel movements from no regular solid bowel movements. Fecal incontinence improved from daily liquid and small solid loss to no stool leakage. CONCLUSIONS: In patients with systemic medical problems contributing to defecatory dysfunction and bowel incontinence, such as cerebral palsy, sacral neuromodulation was found to provide significant relief of bowel symptoms in addition to associated abdominal pain. As a result of intervention, the patient reported significant improvement in quality of life and less limitations due to dyssynergic defecation.

Measuring arterial oxygenation in a high altitude field environment: comparing portable pulse oximetry with blood gas analysis.

OBJECTIVE: High altitude environments present unique medical treatment challenges. Medical providers often use small portable pulse oximetry devices to help guide their clinical decision making. A significant body of high altitude research is based on the use of these devices to monitor hypoxia, yet there is a paucity of evidence that these devices are accurate in these environments. We studied whether these devices perform accurately and reliably under true mountain conditions. METHODS: Healthy unacclimatized active-duty military volunteers participating in mountain warfare training at 2100 m (6900 feet) above sea level were evaluated with several different pulse oximetry devices while in a cold weather, high altitude field environment and then had arterial blood gases (ABG) drawn using an i-STAT for comparison. The pulse oximeter readings were compared with the gold standard ABG readings. RESULTS: A total of 49 individuals completed the study. There was no statistically significant difference between any of the devices and the gold standard of ABG. The best performing device was the PalmSAT (PS) 8000SM finger probe with a mean difference of 2.17% and SD of 2.56 (95% CI, 1.42% to 2.92%). In decreasing order of performance were the PS 8000AA finger probe (mean ± SD, 2.54% ± 2.68%; 95% CI, 1.76% to 3.32%), the PS 8000Q ear probe (2.47% ± 4.36%; 95% CI, 1.21% to 3.75%), the Nonin Onyx 9500 (3.29% ± 3.12%; 95% CI, 2.39% to 4.20%), and finally the PS 8000R forehead reflectance sensor (5.15% ± 2.97%; 95% CI, 4.28% to 6.01%). CONCLUSIONS: Based on the results of this study, results of the newer portable pulse oximeters appear to be closely correlated to that of the ABG measurements when tested in true mountain conditions.

Follicular and luteal phase endometrial thickness and echogenic pattern and pregnancy outcome in oocyte donation cycles.

PURPOSE: To study the effect of endometrial thickness (ET) and echogenic pattern (EP) in oocyte donation cycles upon pregnancy outcomes. METHODS: Seventy-nine cycles resulting in blastocyst embryo transfer were evaluated. Donors underwent ovarian hyperstimulation using rFSH and GnRH-antagonist. Recipients were synchronized to donors using GnRH-agonist down-regulation followed by fixed dose of estrogen (E2) and progesterone (P4) following hCG. Transvaginal ultrasound (US) obtained ET and EP 10-11 days after initiation of E2 and on day of embryo transfer. Primary outcome was ET and EP in pregnant and non-pregnant cycles. Stimulation and embryology data was analyzed in donors to assess differences prior to transfer. RESULTS: Fifty-nine cycles resulted in clinical pregnancy. No differences were observed in pregnant vs. non-pregnant cycles in proliferative or secretory ET and EP. Similar baseline and stimulation characteristics were found in pregnant and non-pregnant cycles. Regression analysis showed end thickness were not predictive of pregnancy outcomes. CONCLUSIONS: Endometrial characteristics in recipients prior to and following progesterone were not predictive of pregnancy outcomes.

Primary genitourinary melanoma presenting as voiding dysfunction.

A case of primary malignant melanoma of the urethra in a 67-year-old female is presented. Cystourethroscopy performed during a workup for pelvic organ prolapse revealed a bladder and urethral mass. Initial histologic examination was interpreted as undifferentiated sarcoma; however, after immunohistochemical staining by two separate institutions, malignant melanoma was diagnosed. Being rare, urethral melanoma is often misdiagnosed, and treatment can be delayed. Given its poor prognosis, early diagnosis is essential, and clinicians need to include it in their differential when working up a patient with genitourinary complaint.

Attitudes and perceptions regarding subspecialty training in female pelvic medicine and reconstructive surgery.

The objective of the study was to evaluate perceptions regarding subspecialty training in female pelvic medicine and reconstructive surgery (FPMRS) in the United States. A 57-item questionnaire was anonymously mailed to fellows and applicants to FPMRS fellowship. Seventy-four American fellowship interviewees and current fellows completed the entire questionnaire (56% response rate). Key factors associated with higher interest in FPMRS compared to general obstetrics and gynecology (OBG) included competitiveness to get into fellowship and new developments. Key factors associated with higher interest in FPMRS compared to other subspecialties in obstetrics and gynecology (SUB) were lower risk of malpractice and higher sense of career satisfaction. Commonly cited attributes of FPMRS that attract to the field relate to the complexity of cases and the quantity of time spent in the operating room. Majority of responders preferred academics over private practice or a mixture (55.4%, 17.6%, and 27%, respectively). The most important reason for interest in FPMRS compared to OBG and SUB is quality time in the operating room and lower risk of malpractice, respectively. Results of this study may help attract medical students to OBG and help mentors with career counseling.

Overcoming the challenging cervix: techniques to access the uterine cavity.

OBJECTIVE: To identify cervical stenosis and review medical, surgical, and radiological modalities to access the uterine cavity. MATERIALS AND METHODS: Computerized searches of Medline and PubMed from 1996 to 2005 were conducted using the key words "cervix," "cervical ripening," and "cervical stenosis." References from identified publications were manually searched and cross-referenced to identify additional relevant articles. We review relevant techniques on how to access the uterine cavity when cervical stenosis is encountered. RESULTS: Many gynecologic procedures require uncomplicated access through the cervix to access the uterine cavity, including hysteroscopy, dilation and curettage, sonohysterogram, hysterosalpingogram, endometrial biopsy, and embryo transfer for in vitro fertilization. These procedures can be quite complicated when a cervix is obstructed. Management techniques described include the medical use of misoprostol and laminaria, intraoperative ultrasound guidance, and operative creation of a new passage. Additionally, techniques for bypassing the obstructed cervix and preventing cervical stenosis have been described. CONCLUSIONS: Cervical stenosis can result in iatrogenic complications. Preoperative identification, cervical ripening agents, osmotic dilators, and the use of ultrasound guidance are useful in overcoming cervical stenosis. It is also key to identify those at risk for cervical stenosis and implement preventative techniques as needed.

Clinical response of three whitening products having different peroxide delivery: comparison of tray, paint-on gel, and dentifrice.

OBJECTIVE: Comparative clinical research was conducted to evaluate the efficacy and safety of three peroxide-containing tooth whitening products having different peroxide delivery. METHODOLOGY: A total of 43 healthy adults who met entrance criteria were randomly assigned to either a dual-phase, anticavity, 1% hydrogen peroxide dentifrice with a manganese gluconate activator, an 18% carbamide peroxide paint-on gel, or a 5% carbamide peroxide professional custom tray system. Following manufacturer's instructions, the activated dentifrice was used at least twice daily for two minutes, while the paint-on gel was applied twice daily. The custom tray, a barrier system and the experimental control for this study, was worn continuously for six to eight hours daily. Tooth color (L*a*b*) was measured on the maxillary anterior teeth from standard digital images, while safety was assessed from examination and subject report. RESULTS: At Day 15, the custom tray group had a significant (p < 0.002) reduction in yellowness and increased lightness, with adjusted mean (SE) deltab* of -1.83 (0.210) and deltaL* of 1.45 (0.292). The custom tray group experienced on average greater color improvement compared to either the paint-on gel or activated peroxide whitening dentifrice, differing significantly (p < 0.01) from either of the barrier-free systems with respect to deltab*, deltaL*, deltaE*, and deltaW*. In comparison, 14-days' use of the paint-on gel and activated dentifrice did not result in significant (p > 0.10) color improvements from baseline for deltab*, deltaL*, or deltaW*, with these two barrier-free systems not differing significantly (p > 0.26) with respect to any individual or composite color parameters. Tooth sensitivity and oral irritation were the most common safety findings in the tray and dentifrice groups (there were no adverse events in the paint-on group), and no subject discontinued treatment early because of a treatment-related adverse event. CONCLUSION: In head-to-head 14-day testing, a low concentration (5% carbamide peroxide) barrier-based tray system yielded superior tooth color improvement compared to two barrier-free delivery systems-an 18% carbamide peroxide paint-on gel and a 1% hydrogen peroxide dentifrice with a metal activator.

Placebo-controlled clinical trial evaluating a 10% hydrogen peroxide whitening strip.

OBJECTIVE: A placebo-controlled clinical trial was conducted to evaluate the effectiveness and safety of a 10% hydrogen peroxide strip-based whitening system in subjects with tooth discoloration and no previous history of tooth whitening. METHODOLOGY: Informed consent was obtained, and 39 healthy adults were randomly assigned to either 10% hydrogen peroxide whitening strips (Crest Whitestrips Premium) or placebo strips with no peroxide. Strips were used unsupervised twice daily for 30 minutes over a seven-day period. At day four and day eight, tooth color (L*a*b*) was measured on the maxillary anterior teeth from standard digital images, and safety was assessed from examinations and subject reports. RESULTS: After three treatment days, the 10% hydrogen peroxide strip group had significant (p < 0.0001) color improvement from baseline, with means (SD) for deltab* and deltaL* of -1.57 (0.472) and 1.72 (0.619), respectively. Continued strip use from day four to day eight resulted in significant (p < 0.002) incremental improvement in both yellowness and lightness. By the end of treatment (day eight), the adjusted mean (SE) color change between groups was -2.20 (0.275) for deltab* and 2.24 (0.254) for deltaL*, a highly significant (p < 0.0001) color improvement for the 10% hydrogen peroxide group relative to placebo, of similar absolute magnitude for deltab* and deltaL*. Treatment with the 10% hydrogen peroxide strips was well-tolerated, with tooth sensitivity and oral irritation representing the most common findings. CONCLUSION: In this double-blind, placebo-controlled clinical trial, statistically significant tooth whitening was evident after three days' treatment with 10% hydrogen peroxide whitening strips, and color improved with continued usage over seven days.

Two heteromeric Kv1 potassium channels differentially regulate action potential firing.

Low-threshold voltage-gated potassium currents (I(LT)) activating close to resting membrane potentials play an important role in shaping action potential (AP) firing patterns. In the medial nucleus of the trapezoid body (MNTB), I(LT) ensures generation of single APs during each EPSP, so that the timing and pattern of AP firing is preserved on transmission across this relay synapse (calyx of Held). This temporal information is critical for computation of sound location using interaural timing and level differences. I(LT) currents are generated by dendrotoxin-I-sensitive, Shaker-related K+ channels; our immunohistochemistry confirms that MNTB neurons express Kv1.1, Kv1.2, and Kv1.6 subunits. We used subunit-specific toxins to separate I(LT) into two components, each contributing approximately one-half of the total low-threshold current: (1) I(LTS), a tityustoxin-Kalpha-sensitive current (TsTX) (known to block Kv1.2 containing channels), and (2) I(LTR), an TsTX-resistant current. Both components were sensitive to the Kv1.1-specific toxin dendrotoxin-K and were insensitive to tetraethylammonium (1 mm). This pharmacological profile excludes homomeric Kv1.1 or Kv1.2 channels and is consistent with I(LTS) channels being Kv1.1/Kv1.2 heteromers, whereas I(LTR) channels are probably Kv1.1/Kv1.6 heteromers. Although they have similar kinetic properties, I(LTS) is critical for generating the phenotypic single AP response of MNTB neurons. Immunohistochemistry confirms that Kv1.1 and Kv1.2 (I(LTS) channels), but not Kv1.6, are concentrated in the first 20 microm of MNTB axons. Our results show that heteromeric channels containing Kv1.2 subunits govern AP firing and suggest that their localization at the initial segment of MNTB axons can explain their dominance of AP firing behavior.