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Objectives: We recently reported that percutaneous peripheral nerve stimulation (PNS or "neuromodulation") decreased pain and opioid consumption within the first two weeks following ambulatory surgery. However, the anatomic lead locations were combined for the analysis, and benefits for each location remain unknown. We therefore now report the effects of percutaneous PNS for brachial plexus and sciatic nerve leads separately., Materials and Methods: Before surgery, leads were implanted percutaneously to target the brachial plexus (N = 21) for rotator cuff repair or sciatic nerve (N = 40) for foot/ankle surgery, followed by a single injection of local anesthetic. Postoperatively, subjects were randomized in a double masked fashion to 14 days of electrical stimulation (N = 30) or sham/placebo (N = 31) using an external pulse generator. The primary outcome of interest was opioid consumption and pain scores evaluated jointly. Thus, stimulation was deemed effective if superior on either outcome and at least noninferior on the other., Results: For brachial plexus leads, during the first seven postoperative days pain measured with the numeric rating scale in participants given active stimulation was a median [interquartile range] of 0.8 [0.5, 1.6] versus 3.2 [2.7, 3.5] in patients given sham (p < 0.001). For this same group, opioid consumption in participants given active stimulation was 10 mg [5, 20] versus 71 mg [35, 125] in patients given sham (p = 0.043). For sciatic nerve leads, pain scores for the active treatment group were 0.7 [0, 1.4] versus 2.8 [1.6, 4.6] in patients given sham (p < 0.001). During this same period, participants given active stimulation consumed 5 mg [0, 30] of opioids versus 40 mg [20, 105] in patients given sham (p = 0.004). Treatment effects did not differ statistically between the two locations., Conclusions: Ambulatory percutaneous PNS of both the brachial plexus and sciatic nerve is an effective treatment for acute pain free of systemic side effects following painful orthopedic surgery., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Low back pain (LBP) is the leading cause of disability in the United States and the main reason for absenteeism. Successful management of chronic LBP (CLBP) is dependent on multimodal evidence-based interventions. Digital interventions (DI) may ease accessibility to such treatments, increasing adherence, while reducing healthcare-related costs., Objectives: Assess the impact of a completely remote multimodal DI on productivity impairment in a real-work context cohort of patients with CLBP., Design: Longitudinal study., Methods: Ad-hoc analysis of an interventional, single-arm study of individuals with CLBP undergoing a DI for 12 weeks. Outcomes included the mean change in work productivity and activity impairment (including overall and non-work related activities), pain, depression, anxiety, fear-avoidance beliefs, analgesic usage, and engagement. Minimal clinically important change (MCIC) was calculated for productivity using anchor- and distribution-based methods., Results: From 560 patients at program start, 78.4% completed the DI. A significant improvement in overall productivity (20.21, 95%CI: 16.48-23.94) and in non-work related activities (21.36, 95%CI: 17.49-25.22) was observed, corresponding to a responder rate of 57.1-83.3% and 60.5-79.8%, respectively, and depending on the MCIC method. Significant improvements were reported for pain (2.32 points, 95%CI: 2.02-2.61), anxiety (5.24, 95%CI: 4.18-6.29), depression (6.38, 95%CI: 4.78-7.98) and fear-avoidance beliefs (8.11, 95%CI: 6.20-10.02). Both engagement (sessions per week) and patient satisfaction scores were high, 2.9 (SD 1.0) and 8.8/10 (SD 1.6), respectively., Conclusions: This study demonstrated the utility of a multimodal DI to address productivity impairment. DIs have great potential to ease the burden of CLBP, providing an accessible and cost-effective modality of care., Trial Registration: The study was approved by the New England IRB (protocol number 120190313) and prospectively registered in ClinicalTrials.gov, NCT04092946, on September 17th, 2019., Competing Interests: Declaration of competing interest Anabela C. Areias, Dora Janela, Fabíola Costa, Maria Molinos, Virgílio Bento, Fernando Correia, and Vijay Yanamadala are employees at SWORD Health, the study sponsor. Justin Scheer, Robert Moulder, Jorge Lains and Steve Cohen received a scientific advisor honorarium from SWORD Health., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: External defibrillators are used for arrhythmia cardioversion and for defibrillating during cardiac arrest. During defibrillation, short-duration biphasic pulses cause intense motion due to rapid chest-wall muscle contraction. A reduced motion external defibrillator (RMD) was constructed by integrating a commercial defibrillator with a Tetanizing-waveform generator. A long-duration, low-amplitude, tetanizing waveform slowly stimulated the chest musculature before the biphasic pulse, reducing muscle contraction during the shock., Objective: The purpose of this study was to evaluate RMD defibrillation in swine for subject motion during defibrillation pulses and for defibrillation effectiveness. RMD defibrillation can reduce the duration of arrhythmia ablation therapy or simplify cardioversion procedures., Methods: The tetanizing unit delivered a triangular 1-kHz pulse of 0.25- to 2.0-second duration and 10- to 100-V peak amplitude, subsequently triggering the conventional defibrillator to output standard 1- to 200-J energy biphasic pulses at the next R wave. Forward limb motion was evaluated by measuring peak acceleration and limb work during RMD (tetanizing + biphasic) or biphasic pulse-only waveforms at 10 -3 -second sampling rate. Seven swine were arrested electrically and subsequently defibrillated. Biphasic pulse-only and RMD defibrillations were repeated 25-35 times per swine, varying tetanizing parameters and biphasic pulse energy. Defibrillation thresholds (DFTs) were established by measuring the minimum energy required to restore sinus rhythm with biphasic pulse-only or RMD defibrillations., Results: Two forward-limb acceleration peaks occurred during both the tetanizing waveform and biphasic pulse, indicating rapid and slower nociceptic (pain sensation) nerve fiber activation. Optimal RMD tetanizing parameters (25-35 V, 0.25- to 0.75-second duration), relative to biphasic pulse-only defibrillations, resulted in 74% ± 10% smaller peak accelerations and 85% ± 10% reduced limb work. DFT energies were identical when comparing RMD to biphasic pulse-only defibrillations., Conclusion: Relative to conventional defibrillations, RMD defibrillations maintain rhythm restoration efficiency with drastically reduced subject motion., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Low back pain covers a spectrum of different types of pain (eg, nociceptive, neuropathic and nociplastic, or non-specific) that frequently overlap. The elements comprising the lumbar spine (eg, soft tissue, vertebrae, zygapophyseal and sacroiliac joints, intervertebral discs, and neurovascular structures) are prone to different stressors, and each of these, alone or in combination, can contribute to low back pain. Due to numerous factors related to low back pain, and the low specificity of imaging and diagnostic injections, diagnostic methods for this condition continue to be a subject of controversy. The biopsychosocial model posits low back pain to be a dynamic interaction between social, psychological, and biological factors that can both predispose to and result from injury, and should be considered when devising interdisciplinary treatment plans. Prevention of low back pain is recognised as a pivotal challenge in high-risk populations to help tackle high health-care costs related to therapy and rehabilitation. To a large extent, therapy depends on pain classification, and usually starts with self-care and pharmacotherapy in combination with non-pharmacological methods, such as physical therapies and psychological treatments in appropriate patients. For refractory low back pain, a wide range of non-surgical (eg, epidural steroid injections and spinal cord stimulation for neuropathic pain, and radiofrequency ablation and intra-articular steroid injections for mechanical pain) and surgical (eg, decompression for neuropathic pain, disc replacement, and fusion for mechanical causes) treatment options are available in carefully selected patients. Most treatment options address only single, solitary causes and given the complex nature of low back pain, a multimodal interdisciplinary approach is necessary. Although globally recognised as an important health and socioeconomic challenge with an expected increase in prevalence, low back pain continues to have tremendous potential for improvement in both diagnostic and therapeutic aspects. Future research on low back pain should focus on improving the accuracy and objectivity of diagnostic assessments, and devising treatment algorithms that consider unique biological, psychological, and social factors. High-quality comparative-effectiveness and randomised controlled trials with longer follow-up periods that aim to establish the efficacy and cost-effectiveness of low back pain management are warranted., Competing Interests: Declaration of interests SPC reports personal fees from SPR Therapeutics; grants and personal fees from Avanos; grants and personal fees from Scilex/Sorrento; personal fees from Persica; and personal fees from the Department of Justice, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Neuromodulation is an expanding area of pain medicine that incorporates an array of non-invasive, minimally invasive, and surgical electrical therapies. In this Series paper, we focus on spinal cord stimulation (SCS) therapies discussed within the framework of other invasive, minimally invasive, and non-invasive neuromodulation therapies. These therapies include deep brain and motor cortex stimulation, peripheral nerve stimulation, and the non-invasive treatments of repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation. SCS methods with electrical variables that differ from traditional SCS have been approved. Although methods devoid of paraesthesias (eg, high frequency) should theoretically allow for placebo-controlled trials, few have been done. There is low-to-moderate quality evidence that SCS is superior to reoperation or conventional medical management for failed back surgery syndrome, and conflicting evidence as to the superiority of traditional SCS over sham stimulation or between different SCS modalities. Peripheral nerve stimulation technologies have also undergone rapid development and become less invasive, including many that are placed percutaneously. There is low-to-moderate quality evidence that peripheral nerve stimulation is effective for neuropathic pain in an extremity, low quality evidence that it is effective for back pain with or without leg pain, and conflicting evidence that it can prevent migraines. In the USA and many areas in Europe, deep brain and motor cortex stimulation are not approved for chronic pain, but are used off-label for refractory cases. Overall, there is mixed evidence supporting brain stimulation, with most sham-controlled trials yielding negative findings. Regarding non-invasive modalities, there is moderate quality evidence that repetitive transcranial magnetic stimulation does not provide meaningful benefit for chronic pain in general, but conflicting evidence regarding pain relief for neuropathic pain and headaches. For transcranial direct current stimulation, there is low-quality evidence supporting its benefit for chronic pain, but conflicting evidence regarding a small treatment effect for neuropathic pain and headaches. For transcutaneous electrical nerve stimulation, there is low-quality evidence that it is superior to sham or no treatment for neuropathic pain, but conflicting evidence for non-neuropathic pain. Future research should focus on better evaluating the short-term and long-term effectiveness of all neuromodulation modalities and whether they decrease health-care use, and on refining selection criteria and treatment variables., Competing Interests: Declaration of interests SPC has served as a consultant for Avanos, Department of Justice, Persica, and SPR Therapeutics, and his institutions have received grant funding from Scilex & Avanos (Johns Hopkins) and SPR Therapeutics (Walter Reed), including National Institutes for Health funding (1 UH3135804, U24NS115708, R01DA048206–01, and GR101558). MAH served as a consultant for Mainstay Medical, Saluda, and SPR Therapeutics. HK received research supplies from Soterix Medical and National Institutes for Health funding (1 R01 AG068167–01). CH was on the advisory board for Medtronic., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Nociplastic pain is the semantic term suggested by the international community of pain researchers to describe a third category of pain that is mechanistically distinct from nociceptive pain, which is caused by ongoing inflammation and damage of tissues, and neuropathic pain, which is caused by nerve damage. The mechanisms that underlie this type of pain are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles. The symptoms observed in nociplastic pain include multifocal pain that is more widespread or intense, or both, than would be expected given the amount of identifiable tissue or nerve damage, as well as other CNS-derived symptoms, such as fatigue, sleep, memory, and mood problems. This type of pain can occur in isolation, as often occurs in conditions such as fibromyalgia or tension-type headache, or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain, as might occur in chronic low back pain. It is important to recognise this type of pain, since it will respond to different therapies than nociceptive pain, with a decreased responsiveness to peripherally directed therapies such as anti-inflammatory drugs and opioids, surgery, or injections., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chronic pain exerts an enormous personal and economic burden, affecting more than 30% of people worldwide according to some studies. Unlike acute pain, which carries survival value, chronic pain might be best considered to be a disease, with treatment (eg, to be active despite the pain) and psychological (eg, pain acceptance and optimism as goals) implications. Pain can be categorised as nociceptive (from tissue injury), neuropathic (from nerve injury), or nociplastic (from a sensitised nervous system), all of which affect work-up and treatment decisions at every level; however, in practice there is considerable overlap in the different types of pain mechanisms within and between patients, so many experts consider pain classification as a continuum. The biopsychosocial model of pain presents physical symptoms as the denouement of a dynamic interaction between biological, psychological, and social factors. Although it is widely known that pain can cause psychological distress and sleep problems, many medical practitioners do not realise that these associations are bidirectional. While predisposing factors and consequences of chronic pain are well known, the flipside is that factors promoting resilience, such as emotional support systems and good health, can promote healing and reduce pain chronification. Quality of life indicators and neuroplastic changes might also be reversible with adequate pain management. Clinical trials and guidelines typically recommend a personalised multimodal, interdisciplinary treatment approach, which might include pharmacotherapy, psychotherapy, integrative treatments, and invasive procedures., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Many clinical practice guidelines recommend similar approaches for the assessment and management of low back pain. Recommendations include use of a biopsychosocial framework to guide management with initial non-pharmacological treatment, including education that supports self-management and resumption of normal activities and exercise, and psychological programmes for those with persistent symptoms. Guidelines recommend prudent use of medication, imaging, and surgery. The recommendations are based on trials almost exclusively from high-income countries, focused mainly on treatments rather than on prevention, with limited data for cost-effectiveness. However, globally, gaps between evidence and practice exist, with limited use of recommended first-line treatments and inappropriately high use of imaging, rest, opioids, spinal injections, and surgery. Doing more of the same will not reduce back-related disability or its long-term consequences. The advances with the greatest potential are arguably those that align practice with the evidence, reduce the focus on spinal abnormalities, and ensure promotion of activity and function, including work participation. We have identified effective, promising, or emerging solutions that could offer new directions, but that need greater attention and further research to determine if they are appropriate for large-scale implementation. These potential solutions include focused strategies to implement best practice, the redesign of clinical pathways, integrated health and occupational interventions to reduce work disability, changes in compensation and disability claims policies, and public health and prevention strategies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Disease progression in cystic fibrosis (CF) is marked by worsening exercise tolerance. Further, maximal exercise capacity (VO2 peak) correlates with survival in CF, but maximal tests are uncomfortable and resource-intensive. A three-minute step test (STEP) has been validated in CF. Heart rate (HR) recovery after exercise correlates with all-cause mortality in adult non-CF populations. We compared HR recovery after the three-minute step test with VO2 peak in children with CF., Methods: Twenty-four children with CF performed STEP and a maximal exercise test. Correlation between the tests was assessed., Results: Maximum HR on STEP was lower than on the maximal test (140 vs. 190, p<0.01). Peak HR during STEP correlated inversely with VO2 peak. In subjects with mild lung disease, faster HR recovery after STEP correlated with higher VO2 peak., Conclusions: The three-minute step test is a feasible submaximal test in this patient population. HR during and after a three-minute step test may reflect VO2 peak in children with CF., (Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Present treatment methods are often unsatisfactory in reducing post-amputation pain. Peripheral nerve stimulation (PNS) could reduce the pain, but it is rarely used because present methods require invasive surgical access and precise placement of the leads in close proximity (≤ 2 mm) with the nerve., Methods: The present study investigated the feasibility of delivering PNS to patients with moderate-to-severe post-amputation pain in the lower extremity using a fine-wire lead placed percutaneously under ultrasound guidance a remote distance (0.5-3.0 cm) away from the sciatic and/or femoral nerves., Results: Fourteen of the 16 subjects who completed in-clinic testing responded to stimulation, reported ≥ 75% paresthesia coverage, obtained clinically significant pain relief, and proceeded to a two-week home trial with a percutaneous PNS system. Two of the 14 responders had their leads removed early because of accidental dislodgement (N = 2), two had temporary discomfort near the lead (N = 2), and one had return of post-amputation pain despite stimulation (N = 1) and did not complete the home trial. The nine responders who completed the home trial reported reductions in their mean daily worst post-amputation pain (56 ± 26%, 56 ± 26%, N = 9), average residual limb pain (72 ± 28%, 42 ± 27%, N = 7), average phantom limb pain (81 ± 28%, 47 ± 48%, N = 7), residual limb pain interference (81 ± 27%, 53 ± 17%, N = 6), phantom limb pain interference (83 ± 31%, 56 ± 46%, N = 7), and Pain Disability Index (70 ± 38%, 55 ± 32%, N = 9) during the second week of stimulation and four weeks after the end of stimulation, respectively. All nine responders rated their change in quality of life as improved at the end of stimulation and at the end of the four-week follow-up period. Subjects reported minor decreases in the Beck Depression Inventory scores (43 ± 51%, 32 ± 57%, N = 9). Most subjects had no substantial changes other than minor decreases (N = 3) in pain medication., Conclusion: Achievement of significant pain relief and improvements in quality of life with a minimally invasive method of PNS holds promise for providing relief of post-amputation pain., (© 2013 International Neuromodulation Society.)

Background: Anticipation of the types of injuries that occur in modern warfare is essential to plan operations and maintain a healthy military. We aimed to identify the diagnoses that result in most medical evacuations, and ascertain which demographic and clinical variables were associated with return to duty., Methods: Demographic and clinical data were prospectively obtained for US military personnel who had been medically evacuated from Operation Iraqi Freedom or Operation Enduring Freedom (January, 2004-December, 2007). Diagnoses were categorised post hoc according to the International Classification of Diseases codes that were recorded at the time of transfer. The primary outcome measure was return to duty within 2 weeks., Findings: 34 006 personnel were medically evacuated, of whom 89% were men, 91% were enlisted, 82% were in the army, and 86% sustained an injury in Iraq. The most common reasons for medical evacuation were: musculoskeletal and connective tissue disorders (n=8104 service members, 24%), combat injuries (n=4713, 14%), neurological disorders (n=3502, 10%), psychiatric diagnoses (n=3108, 9%), and spinal pain (n=2445, 7%). The factors most strongly associated with return to duty were being a senior officer (adjusted OR 2.01, 95% CI 1.71-2.35, p<0.0001), having a non-battle-related injury or disease (3.18, 2.77-3.67, p<0.0001), and presenting with chest or abdominal pain (2.48, 1.61-3.81, p<0.0001), a gastrointestinal disorder (non-surgical 2.32, 1.51-3.56, p=0.0001; surgical 2.62, 1.69-4.06, p<0.0001), or a genitourinary disorder (2.19, 1.43-3.36, p=0.0003). Covariates associated with a decreased probability of return to duty were serving in the navy or coast guard (0.59, 0.45-0.78, p=0.0002), or marines (0.86, 0.77-0.96, p=0.0083); and presenting with a combat injury (0.27, 0.17-0.44, p<0.0001), a psychiatric disorder (0.28, 0.18-0.43, p<0.0001), musculoskeletal or connective tissue disorder (0.46, 0.30-0.71, p=0.0004), spinal pain (0.41, 0.26-0.63, p=0.0001), or other wound (0.54, 0.34-0.84, p=0.0069)., Interpretation: Implementation of preventive measures for service members who are at highest risk of evacuation, forward-deployed treatment, and therapeutic interventions could reduce the effect of non-battle-related injuries and disease on military readiness., Funding: John P Murtha Neuroscience and Pain Institute, and US Army Regional Anesthesia and Pain Management Initiative., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Chronic pain patients who are treated with opioid therapy represent a significant challenge to medical professionals. When pain recurs in the face of a previously effective opioid regimen, treatment options include dose escalation, opioid rotation, drug holidays, and the addition of adjuvants. Some experts advocate the use of N-methyl-D-aspartate receptor (NMDA-R) antagonists to combat tolerance. Recently, the use of an intravenous (i.v.) ketamine infusion to predict the response to a dextromethorphan (DX) treatment trial has been described. In this study, 56 opioid-exposed patients with recurrent pain were treated with a low-dose (0.1mg/kg) i.v. ketamine test followed by a DX treatment course. Using previously designated cutoff values for a positive response to ketamine (67% or more pain relief) and DX (50% or more pain relief), the sensitivity, specificity, positive predictive value, and negative predictive value for an i.v. ketamine infusion to predict subsequent response to DX treatment were 72%, 68%, 52%, and 85%, respectively. The observed agreement between analgesic responses was 78%, indicating a highly significant correlation (r=0.54, P=0.0001). Subgroup classification revealed no significant differences in the response to either ketamine or DX treatment based on pain classification (i.e., nociceptive, neuropathic, or mixed) or placebo response. In contrast, a weaker correlation between ketamine and DX response was found in subjects requiring high-dose rather than low-dose opioid therapy. A significant correlation also was noted between the development of side effects for the two NMDA-R antagonists. Based on these results, we conclude that an i.v. ketamine test may be a valuable tool in predicting subsequent response to DX treatment in opioid-exposed patients. with persistent pain.

Background: Numerous studies have demonstrated that therapeutic injections carried out to treat a variety of different pain conditions should ideally be performed under radiological guidance because of the propensity for blinded injections to be inaccurate. Although trochanteric bursa injections are commonly performed to treat hip pain, they have never been described using fluoroscopy., Methods: The authors reviewed recorded data on 40 patients who underwent trochanteric bursa injections for hip pain with or without low back pain. The initial needle placement was done blindly, with all subsequent attempts done using fluoroscopic guidance. After bone contact, imaging was used to determine if the needle was positioned on the lateral edge of the greater trochanter (GT). Once this occurred, 1 ml of radiopaque contrast was injected to assess bursa spread., Results: The GT was contacted in 78% of cases and a bursagram obtained in 45% of patients on the first needle placement. In 23% of patients a bursagram was obtained on the second attempt and in another 23% on the third attempt. Four patients (10%) required four or more needle placements before a bursagram was appreciated. Attending physicians obtained a bursagram on the first attempt 53% of the time vs 46% for fellows and 36% for residents (P=0.64). Older patients were more likely to require multiple injections than younger patients., Conclusions: Radiological confirmation of bursal spread is necessary to ensure that the injectate reaches the area of pathology during trochanteric bursa injections.

We describe a case of mucoid impaction following nasotracheal intubation in a child with an upper respiratory infection that was successfully treated with a fiberoptic bronchoscope too large to pass through the endotracheal tube lumen. To the best of our knowledge, it is the first report in the anesthesia literature in which the placement of a nasal tracheal tube is implicated as the cause of the mucous obstruction. The physiologic changes that occur with anesthesia and that place patients at increased risk for this phenomenon, as well as the differential diagnosis, treatment, and prevention of this entity, are discussed.

Escherichia coli single-strand binding protein (SSB), which participates in DNA replication, also plays a role in DNA repair and induction of SOS functions. We show that the formation of RecA-dATP-single-stranded DNA complexes is influenced by the presence of SSB. In equilibrium reactions with limiting bacteriophage fd DNA, the mutant SSB113 protein competes more effectively than SSB with RecA protein for sites on the DNA. This result can account for the inability of strain ssb113 to amplify RecA protein synthesis and induce lambda prophage. SSB fails to displace RecA protein completely, even at very high concentrations. Both proteins inhibit the dATPase activity of RecA protein in spite of a large proportion of RecA protein still complexed to single-stranded DNA. Analysis of the multiple RecA protein activities and how they respond to the presence of SSB suggests that they fall into two distinct classes. Those that are enhanced by SSB (proteolysis and strand assimilation) and those inhibited by SSB (NTPase, reannealing of complementary single-stranded DNA). We propose a two-state model of conformational change of RecA protein, affected by the number of available free bases in single-stranded DNA relative to the number of RecA monomers, that would explain the choice of mutually exclusive catalytic activities.

Estrogen receptor binding studies were performed on cytosol obtained from human benign prostatic hyperplasia (BPH) tissue. Binding assays were done in the absence or presence of various concentrations of phenylmethylsulfonyl fluoride (PMSF). Saturation analysis and Scatchard plots showed that the binding of 17 beta -estradiol to the estrogen receptor (ER) was inhibited by PMSF. The nature of the inhibition appears to be uncompetitive, as determined from double-reciprocal plots. Glycerol density gradient centrifugation analysis also confirmed the results obtained with Scatchard plots. The inhibition observed in the presence of dithiothreitol (DTT) was greater than the inhibition observed in the absence of DTT. The maximum number of binding sites (Bmax) observed in our present study was 59.1 +/- 34.1 fmol/mg protein with an equilibrium dissociation constant (KD) of 2.2 +/- 2.2 nM. Our study indicates that PMSF significantly affects 17 beta -estradiol binding to ER and consequently alters the estimation of ER in Human BPH.