A High Incidence of Perineal Post-Related Complications After Hip Arthroscopy Is Self-Reported by Patients in Anonymous Online Forums.

Purpose: To evaluate online, self-reported pudendal nerve or perineal injuries related to the use of a perineal post during hip arthroscopy. Methods: Public posts on Reddit and the Health Organization for Pudendal Education were searched to identify anonymous individuals reporting symptoms of pudendal nerve or perineal injury following hip arthroscopy. Included posts were by any individual with a self-reported history of hip arthroscopy who developed symptoms of pudendal nerve injury or damage to the perineal soft tissues. Demographic information and details about a person's symptoms and concerns were collected from each post. Descriptive statistics were used to analyze the data. Results: Twenty-three online posts reported on a perineal post-related complication following hip arthroscopy. Sex information was available in 16 (70%) posts (8 male, 8 female). Twenty-two posts reported a sensory injury, and 4 posts reported a motor injury with sexual consequences (sexual dysfunction, dyspareunia, impotence). Symptom duration was available in 15 (65%) posts (8 temporary, 7 permanent). Permanent symptoms included paresthesia of the perineum or genitals (7) and sexual complaints (5). Two posts stated they were counseled preoperatively about the possibility of this injury. Zero patients reported that a postless hip arthroscopy alternative was an option made available to them before surgery. Conclusions: A high incidence of permanent pudendal nerve, perineal skin, and genitourinary/sexual complications are self-reported and discussed online by patients who have undergone post-assisted hip arthroscopy. These patients report being uninformed and undereducated about the possibility of sustaining a post-related complication. No patient reported being informed of postless hip arthroscopy preoperatively. Clinical Relevance: Identifying and evaluating self-reported patient information in online medical forums can provide important information about patient experiences and outcomes.

Cast or Nail? Using a Preference-Based Tool for Shared Decision-Making in Pediatric Femoral Shaft Fracture Treatment.

BACKGROUND: Femoral shaft fractures are common injuries in children 2 to 7 years of age, with treatments ranging from casting to flexible intramedullary nails (FIN). Each treatment has unique attributes and outcomes are overall similar. Given equivalent outcomes, we hypothesized that a shared decision-making process, using adaptive conjoint analysis (ACA), can be used to assess individual family situations to determine ultimate treatment choice. METHODS: An interactive survey incorporating an ACA exercise to elicit the preferences of individuals was created. Amazon Mechanical Turk was used to recruit survey respondents simulating the at-risk population. Basic demographic information and family characteristics were collected. Sawtooth Software was utilized to generate relative importance values of five treatment attributes and determine subjects' ultimate treatment choice. Student's t-test or Wilcoxon rank sum test was used to compare relative importance between groups. RESULTS: The final analysis included 186 subjects with 147 (79%) choosing casting as their ultimate treatment choice, while 39 (21%) chose FIN. Need for second surgery had the highest overall average relative importance (42.0), followed by a chance of serious complications (24.6), time away from school (12.9), effort required by caregivers (11.0), and return to activities (9.6). Most respondents (85%) indicated the generated relative importance of attributes aligned "very well or well" with their preferences. For those who chose casting instead of FIN, the need for secondary surgery (43.9 vs. 34.8, P <0.001) and the chance of serious complications (25.9 vs. 19.6, P <0.001) were the most important factors. In addition, returning to activities, the burden to caregivers, and time away from school were all significantly more important to those choosing surgery versus casting (12.6 vs. 8.7 P <0.001, 12.6 vs. 9.8 P =0.014, 16.6 vs. 11.7 P <0.001, respectively). CONCLUSIONS: Our decision-making tool accurately identified subjects' treatment preferences and appropriately aligned them with a treatment decision. Given the increased emphasis on shared decision-making in health care, this tool may have the potential to improve shared decision-making and family understanding, leading to improved satisfaction rates and overall outcomes. LEVEL OF EVIDENCE: Level-III.

Vertical Extension of the T-Capsulotomy Incision in Hip Arthroscopic Surgery Does Not Affect the Force Required for Hip Distraction: Effect of Capsulotomy Size, Type, and Subsequent Repair.

BACKGROUND: Interportal and T-capsulotomies are popular techniques for exposing femoroacetabular impingement deformities. The difference between techniques with regard to the force required to distract the hip is currently unknown. PURPOSE: To quantify how increasing interportal capsulotomy size, conversion to T-capsulotomy, and subsequent repair affect the force required to distract the hip. STUDY DESIGN: Controlled laboratory study. METHODS: Eight fresh-frozen cadaveric hip specimens were dissected and fixed in a materials testing system, such that pure axial distraction of the iliofemoral ligament could be achieved. The primary outcome measure was the load required to distract the hip to a distance of 6 mm at a rate of 0.5 mm/s. Each hip was tested in the intact state and then sequentially under varying capsulotomy conditions: 2-cm interportal, 4-cm interportal, half-T (4-cm interportal and 2-cm T-capsulotomy), and full-T (4-cm interportal and 4-cm T-capsulotomy). After serial testing, isolated T-limb repair and then subsequent complete repair were performed. Repaired specimens underwent distraction testing as previously stated to assess the ability to restore hip stability to the native profile. Distraction force as well as the relative distraction force (percentage normalized to the intact capsule) were compared between all capsulotomy and repair conditions. RESULTS: Increasing interportal capsulotomy size from 2 to 4 cm resulted in significantly less force required to distract the hip ( P < .001). The largest relative decrease in force was seen between the intact state (274.6 ± 71.2 N; 100%) and 2-cm interportal (209.7 ± 73.2 N; 76.4% ± 15.6%; P = .0008). There was no significant mean difference in distraction force when 4-cm interportal (160.4 ± 79.8 N) was converted to half-T (140.7 ± 73.5 N; P = .270) and then full-T (112.0 ± 70.2 N; P = .204). When compared with the intact state, isolated T-limb repair partially restored stability (177.3 ± 86.3 N; 63.5% ± 19.8%; P < .0001), while complete repair exceeded native values (331.7 ± 103.7 N; 122.7% ± 15.1%; P = .0008). CONCLUSION: The conversion of interportal capsulotomy to T-capsulotomy did not significantly affect the force required to distract the hip in a cadaveric model. However, larger interportal capsulotomies resulted in significant stepwise decreases in distraction force. When performing interportal or T-capsulotomy, the iliofemoral ligament strength is significantly decreased, but complete capsular repair demonstrated the ability to restore joint stability to the native, intact hip. CLINICAL RELEVANCE: Increasing interportal capsulotomy size decreases the force required to distract the hip. In an effort to maximize visualization and minimize the magnitude of iliofemoral ligament fibers cut, many surgeons have moved from extended interportal capsulotomy to T-capsulotomy. Interportal and T-capsulotomies result in equivalent hip distraction, partial capsular repair marginally improves hip stability, and only complete repair has the ability to restore the hip to its native biomechanical profile.

A case report and literature review of daptomycin-induced liver injury.

Daptomycin is a lipopeptide antimicrobial used to treat gram positive organisms including multi-drug resistant infections. It has been shown to occasionally cause abnormalities in liver function but more commonly is associated with elevations in serum creatinine phosphokinase (CK) (Hair and Keam, 2007) [1]. We describe a case where a patient being treated for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with daptomycin developed asymptomatic elevated transaminases without evidence of multiorgan failure, hyperbilirubinemia or elevation of CK levels. Other etiologies for liver injury were considered and ruled out, and after daptomycin was discontinued, the transaminases returned to normal levels. We also provide a review of other cases to date documenting possible cases of daptomycin-induced liver injury.

Early recovery after hip arthroscopy for femoroacetabular impingement syndrome: a prospective, observational study.

The early post-operative course after hip arthroscopy for femoroacetabular impingement syndrome has not been thoroughly characterized or correlated to factors that may influence recovery. The aim of this study was to report on early pain, function and attitudes towards rehabilitation and to determine predictors of early recovery after hip arthroscopy. Sixty-two patients reported pre-operative pain, iHOT-12 (hip functional score), psychological status and other baseline characteristics. Pain, iHOT-12, hip flexion and several other outcomes were measured through 6 weeks post-operative. Baseline characteristics were correlated with outcomes using univariate and multivariable models. Pain relief started on post-operative day 1 and consistently improved throughout the 6 weeks of follow-up. The average patient's pain was reduced from a pre-operative level of 5/10 to 2/10 by 6 weeks post-operative. Similarly, iHOT-12 improved from 33/100 to 57/100 whereas hip flexion increased by 9° by 6 weeks post-operative. At 2 weeks post-operative, pre-operative anti-inflammatory usage was associated with greater improvement in pain and swelling; pre-operative opioid usage with poorer patient-reported helpfulness of and adherence to rehabilitation; and higher ASA (American Society of Anesthesiologists) score and lower procedure time with improvement of the pre-operative pain complaint. At 6 weeks, greater depression was associated with lower post-operative pain reduction but greater pre-operative pain complaint improvement. Continuous passive motion usage was associated with increased hip flexion. Pain improved from pre-operative by Day 1 after hip arthroscopy, and early functional improvements were seen by 6 weeks post-operative. Pre-operative anti-inflammatory and opioid usage, depression, race, ASA score, procedure time and continuous passive motion usage were significantly associated with study outcomes.

Arthroscopic hip preservation surgery practice patterns: an international survey.

To design and conduct a survey analyzing pre-, intra- and post- hip arthroscopy practice patterns among hip arthroscopists worldwide. A 21-question, IRB-exempt, HIPAA-compliant, cross-sectional survey was conducted via email using SurveyMonkey to examine pre-operative evaluation, intra-operative techniques and post-operative management. The survey was administered internationally to 151 hip arthroscopists identified from publicly available sources. Seventy-five respondents completed the survey (151 ± 116 hip arthroscopy procedures per year; 8.6 ± 7.1 years hip arthroscopy experience). Standing AP pelvis, false profile and Dunn 45 were the most common radiographs utilized. CT scans were utilized by 54% of surgeons at least some of the time. Only 56% of participants recommended an arthrogram with MRI. Nearly all surgeons either never (40%) or infrequently (58%) performed arthroscopy in Tönnis grade-2 or grade-3 osteoarthritis. Surgeons rarely performed hip arthroscopy on patients with dysplasia (51% never; 44% infrequently). Only 25% of participants perform a routine 'T' capsulotomy and 41% close the capsule if the patient is at risk for post-operative instability. Post-operatively, 52% never use a brace, 39% never use a continuous passive motion, 11% never recommended heterotopic ossification prophylaxis and 30% never recommended formal thromboembolic disease prophylaxis. Among a large number of high-volume experienced hip arthroscopists worldwide, pre-, intra- and post- hip arthroscopy practice patterns have been established and reported. Within this cohort of respondents, several areas of patient evaluation and management remain discordant and controversial without universal agreement. Future research should move beyond expert opinion level V evidence towards high-quality appropriately designed and conducted investigations.

The Warwick Agreement on femoroacetabular impingement syndrome (FAI syndrome): an international consensus statement.

The 2016 Warwick Agreement on femoroacetabular impingement (FAI) syndrome was convened to build an international, multidisciplinary consensus on the diagnosis and management of patients with FAI syndrome. 22 panel members and 1 patient from 9 countries and 5 different specialties participated in a 1-day consensus meeting on 29 June 2016. Prior to the meeting, 6 questions were agreed on, and recent relevant systematic reviews and seminal literature were circulated. Panel members gave presentations on the topics of the agreed questions at Sports Hip 2016, an open meeting held in the UK on 27-29 June. Presentations were followed by open discussion. At the 1-day consensus meeting, panel members developed statements in response to each question through open discussion; members then scored their level of agreement with each response on a scale of 0-10. Substantial agreement (range 9.5-10) was reached for each of the 6 consensus questions, and the associated terminology was agreed on. The term 'femoroacetabular impingement syndrome' was introduced to reflect the central role of patients' symptoms in the disorder. To reach a diagnosis, patients should have appropriate symptoms, positive clinical signs and imaging findings. Suitable treatments are conservative care, rehabilitation, and arthroscopic or open surgery. Current understanding of prognosis and topics for future research were discussed. The 2016 Warwick Agreement on FAI syndrome is an international multidisciplinary agreement on the diagnosis, treatment principles and key terminology relating to FAI syndrome.Author note The Warwick Agreement on femoroacetabular impingement syndrome has been endorsed by the following 25 clinical societies: American Medical Society for Sports Medicine (AMSSM), Association of Chartered Physiotherapists in Sports and Exercise Medicine (ACPSEM), Australasian College of Sports and Exercise Physicians (ACSEP), Austian Sports Physiotherapists, British Association of Sports and Exercise Medicine (BASEM), British Association of Sport Rehabilitators and Trainers (BASRaT), Canadian Academy of Sport and Exercise Medicine (CASEM), Danish Society of Sports Physical Therapy (DSSF), European College of Sports and Exercise Physicians (ECOSEP), European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA), Finnish Sports Physiotherapist Association (SUFT), German-Austrian-Swiss Society for Orthopaedic Traumatologic Sports Medicine (GOTS), International Federation of Sports Physical Therapy (IFSPT), International Society for Hip Arthroscopy (ISHA), Groupo di Interesse Specialistico dell'A.I.F.I., Norwegian Association of Sports Medicine and Physical Activity (NIMF), Norwegian Sports Physiotherapy Association (FFI), Society of Sports Therapists (SST), South African Sports Medicine Association (SASMA), Sports Medicine Australia (SMA), Sports Doctors Australia (SDrA), Sports Physiotherapy New Zealand (SPNZ), Swedish Society of Exercise and Sports Medicine (SFAIM), Swiss Society of Sports Medicine (SGMS/SGSM), Swiss Sports Physiotherapy Association (SSPA).

Blood pressure measurement in the geriatric population.

As the population above 60 years of age is the fastest growing and hypertension is highly prevalent in this group, accurate blood pressure (BP) measurement in the elderly is a very important and widely applicable subject. As with any other population, an accurate measurement of BP is essential to plan therapy and this remains an important consideration in the elderly as well. There are some unique problems of BP measurement in the elderly, including drug-induced orthostatic hypotension, white-coat hypertension, and advanced atherosclerotic disease with stiff arteries. For clinical use, home blood pressure monitoring (HBPM), office measurement, and ambulatory blood pressure monitoring all play a role in patient management. In the office setting, aneroid devices, hybrid devices with electronic transducers, and oscillometric devices are available; all of these require frequent calibration, well-trained operators and technically sound execution. Because the white-coat effect is common in this group, there is a good case for the use of HBPM, which could also be used to detect orthostatic changes at home. Also, HBPM predicts cardiovascular events better than clinical BP, and is also useful in monitoring treatment. Ambulatory blood pressure monitoring provides the most precise assessment of BP over an extended period, but is more complex and expensive. Finally, the utility of noninvasive central arterial pressure through radial artery applanation tonometry, especially in patients with resistant hypertension and likely in the elderly because of advanced atherosclerotic disease and stiff arteries, may prove to be a useful tool to guide or modify drug therapy in the future and requires further study.

Pre-clinical properties of the alpha4beta2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical efficacy for nicotine dependence.

BACKGROUND AND PURPOSE: Smoking cessation trials with three high-affinity partial agonists of alpha4beta2 neuronal nicotinic acetylcholine receptors (nAChRs) have demonstrated differences in their clinical efficacy. This work examines the origin of the differences by taking into account brain exposure and pharmacological effects at human alpha4beta2 nAChRs. EXPERIMENTAL APPROACH: Rat plasma and brain pharmacokinetics were characterized and used to predict human steady-state plasma and brain concentrations following recommended doses of each of the three compounds. The pharmacological characterization included in vitro affinities at different nAChR subtypes, functional efficacies and potencies at the human alpha4beta2 nAChR, as well as in vivo effects on rat mesolimbic dopamine turn-over. KEY RESULTS: A comparison of predicted human brain concentrations following therapeutic doses demonstrated that varenicline and nicotine, but not dianicline and cytisine, can extensively desensitize and, to a lesser extent, activate alpha4beta2 nAChRs. The limited clinical efficacy of dianicline may be accounted for by a combination of weak functional potency at alpha4beta2 nAChRs and moderate brain penetration, while recommended doses of cytisine, despite its high in vitro potency, are predicted to result in brain concentrations that are insufficient to affect alpha4beta2 nAChRs. CONCLUSIONS AND IMPLICATIONS: The data provide a plausible explanation for the higher abstinence rate in smoking cessation trials following treatment with varenicline than with the two other alpha4beta2 nAChR partial agonists. In addition, this retrospective analysis demonstrates the usefulness of combining in vitro and in vivo parameters with estimated therapeutic human brain concentrations for translation to clinical efficacy.

The financial impact of orthopaedic fellowship training.

BACKGROUND: Previous reports have compared the expected financial return of a medical education with those expected in other professions. However, we know of no published report estimating the financial return of orthopaedic training. The purpose of this study was to estimate the financial incentives that may influence the decision to invest an additional year of training in each of the major orthopaedic fellowships. METHODS: With survey data from the American Academy of Orthopaedic Surgeons and using standard financial techniques, we calculated the estimated return on investment of an additional year of orthopaedic training over a working lifetime. The net present value, internal rate of return, and the break-even point were estimated. Eight fellowships were examined and compared with general orthopaedic practice. RESULTS: Investment in an orthopaedic fellowship yields variable returns. Adult spine, shoulder and elbow, sports medicine, hand, and adult arthroplasty may yield positive returns. Trauma yields a neutral return, while pediatrics and foot and ankle have negative net present values. On the basis of mean reported incomes, the break-even point was two years for spine, seven years for hand, eight years for shoulder and elbow, twelve years for adult arthroplasty, thirteen years for sports medicine, and twenty-seven years for trauma. Fellowship-trained pediatric and foot and ankle surgeons did not break even following the initial investment. When working hours were controlled for, the returns for adult arthroplasty and trauma became negative. CONCLUSIONS: The financial return of an orthopaedic fellowship varies on the basis of the specialty chosen. While reasons to pursue fellowship training vary widely, and many are not financial, there are positive and negative financial incentives. Therefore, the decision to pursue fellowship training is best if it is not made on the basis of financial incentives. This information may assist policy makers in analyzing medical education economics to ensure the training of orthopaedic surgeons in all specialties and subspecialties.

Steroid-responsive large vessel vasculitis: application of whole-brain 320-detector row dynamic volume CT angiography and perfusion.

SUMMARY: A patient with suspected giant cell arteritis and prior negative findings on superficial temporal artery biopsy was evaluated with 320-detector row CT angiography (CTA) and whole-brain perfusion. Corticosteroid treatment was initiated on the basis of CT angiography findings of arteritis and a cortical perfusion deficit. The patient's symptoms and perfusion imaging findings resolved following therapy. Whole-brain CTA and imaging was helpful in the diagnosis and monitoring this patient with suspected vasculitis.

Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid.

The preclinical pharmacology of the alpha4beta2 nicotinic acetylcholine receptor (nAChR) partial agonist varenicline, a novel smoking cessation agent is described. Varenicline binds with subnanomolar affinity only to alpha4beta2 nAChRs and in vitro functional patch clamp studies in HEK cells expressing nAChRs show that varenicline is a partial agonist with 45% of nicotine's maximal efficacy at alpha4beta2 nAChRs. In neurochemical models varenicline has significantly lower (40-60%) efficacy than nicotine in stimulating [(3)H]-dopamine release from rat brain slices in vitro and in increasing dopamine release from rat nucleus accumbens in vivo, while it is more potent than nicotine. In addition, when combined with nicotine, varenicline effectively attenuates the nicotine-induced dopamine release to the level of the effect of varenicline alone, consistent with partial agonism. Finally, varenicline reduces nicotine self-administration in rats and supports lower self-administration break points than nicotine. These data suggest that varenicline can reproduce to some extent the subjective effects of smoking by partially activating alpha4beta2 nAChRs, while preventing full activation of these receptors by nicotine. Based on these findings, varenicline was advanced into clinical development and recently shown to be an effective and safe aid for smoking cessation treatment.

Developments in textiles.

The use of biomedical textiles is expanding as a result of innovations in medical procedures and textile technology, and the miniaturisation of electronic devices. Some of their extending capabilities are described here.

Oil removal from used sorbents using a biosurfactant.

Oil spills impose serious damage on the environment. Mechanical recovery by the help of oil sorbents is one of the most important countermeasures in oil spill response. Most sorbents, however, end up in landfills or in incineration after a single use. These options either produce another source of pollution or increase the oil recovery cost. In this study a biosurfactant was used to clean used oil sorbents. This use of biosurfactants is new. Washing parameters tested included sorbent type, washing time, surfactant dosage and temperature. It was found that with biosurfactant washing more than 95% removal of the oil from sorbents was achieved, depending on the washing conditions. Biosurfactants were found to have considerable potential for recycling the used sorbents.

Characterization of water-in-crude oil emulsions in oil spill response.

The formation of water-in-crude oil emulsions occurs when crude oils are spilled into sea. The water-in-crude oil emulsions significantly change the properties of the spilled crude oils and in turn influence the choices made relating to oil spill countermeasures. The water-in-crude oil emulsions were characterized using various techniques in this study. The environmental scanning electron microscopy observation of water droplets in the emulsions is also presented. It is a powerful tool in emulsion observations.

Evaluation of nonwoven polypropylene oil sorbents in marine oil-spill recovery.

Mechanical recovery of oil by oil sorbents is one of the most important countermeasures in marine oil-spill response. Polypropylene is the ideal material for marine oil-spill recovery due to its low density, low water uptake and excellent physical and chemical resistance. Different forms of polypropylene nonwoven sorbents were evaluated in this study in terms of initial oil-sorption capacities and oil-retention properties. The investigation revealed that the fibre diameter, sorbent porosity and oil property are the most important factors in the oil-sorption performance of polypropylene nonwoven sorbents.

Effect of food on the pharmacokinetics of oral MMI270B (CGS 27023A), a novel matrix metalloproteinase inhibitor.

MMI270B is a matrix metalloproteinase inhibitor (MMPI) with in vitro and in vivo activity. To exert optimal target inhibition, MMPI must be given chronically, and therefore, oral bioavailability is important. We analyzed the effect of food intake on AUC0-8 h, Cmax, and Tmax. Seventeen patients were entered into the study. Doses of MMI270B were 150, 400, and 600 mg. The first day, patients ingested the drug in a fasted state and were not allowed to eat for 2 h. The second day, patients ingested the drug 30 min after a light breakfast. Mean AUC0-8 h was not significantly influenced by food intake. Plasma concentrations were well above the IC50 of several MMPs at all doses tested. Mean Cmax was significantly decreased after food intake. Mean Tmax was significantly delayed after food intake. Food intake did not result in a significant change in exposure to MMI270B (AUC0-8 h) but did result in a significant, although not clinically relevant, decrease in peak plasma levels and time to reach peak plasma levels. No specific guidelines concerning the ingestion of MMI270B in either a fed or a fasted state are recommended.

Cloning, structural characterization, and chromosomal localization of the gene encoding the human prostaglandin E(2) receptor EP2 subtype.

Northern blot analysis of human placental RNA using a probe to the 5' end of the human prostaglandin E(2) (PGE(2)) EP2 receptor subtype coding region revealed the existence of a high abundance, low molecular weight transcript. To investigate the origin of this transcript, and its possible relationship to the human EP2 mRNA, we have cloned and characterized the gene encoding the human PGE(2) EP2 receptor subtype, identified transcriptional initiation and termination sites in two tissues (spleen and thymus), and determined its chromosomal localization. The human EP2 gene consists of two exons separated by a large intron, utilizes a common initiation site in both spleen and thymus at 1113 bp upstream of the translation initiation site, and has 3' transcript termini at 1140 bp and 1149 bp downstream of the translation stop site in spleen and thymus respectively. Southern and fluorescence in situ hybridization analysis demonstrated the human EP2 gene to be a single copy gene located in band 22 of the long arm of chromosome 14 (14q22). Though our initial interest in this gene was to investigate potential differential splicing of the human EP2 gene in placenta, this work demonstrates that the atypical transcript observed in placenta probably arises from a distinct, yet related, gene. Knowledge of the sequence, structure, and transcription events associated with the human EP2 gene will enable a broader understanding of its regulation and potential role in normal physiology and disease.

UK-78,282, a novel piperidine compound that potently blocks the Kv1.3 voltage-gated potassium channel and inhibits human T cell activation.

1. UK-78,282, a novel piperidine blocker of the T lymphocyte voltage-gated K+ channel, Kv1.3, was discovered by screening a large compound file using a high-throughput 86Rb efflux assay. This compound blocks Kv1.3 with a IC50 of approximately 200 nM and 1:1 stoichiometry. A closely related compound, CP-190,325, containing a benzyl moiety in place of the benzhydryl in UK-78,282, is significantly less potent. 2 Three lines of evidence indicate that UK-78,282 inhibits Kv1.3 in a use-dependent manner by preferentially blocking and binding to the C-type inactivated state of the channel. Increasing the fraction of inactivated channels by holding the membrane potential at - 50 mV enhances the channel's sensitivity to UK-78,282. Decreasing the number of inactivated channels by exposure to approximately 160 mM external K+ decreases the sensitivity to UK-78,282. Mutations that alter the rate of C-type inactivation also change the channel's sensitivity to UK-78,282 and there is a direct correlation between tau(h) and IC50 values. 3. Competition experiments suggest that UK-78,282 binds to residues at the inner surface of the channel overlapping the site of action of verapamil. Internal tetraethylammonium and external charybdotoxin do not compete UK-78,282's action on the channel. 4. UK-78,282 displays marked selectivity for Kv1.3 over several other closely related K+ channels, the only exception being the rapidly inactivating voltage-gated K+ channel, Kv1.4. 5. UK-78,282 effectively suppresses human T-lymphocyte activation.