A randomized controlled trial investigating the value of patient-specific instrumentation for total knee arthroplasty in the Canadian healthcare system.

AIMS: The purpose of the present study was to compare patient-specific instrumentation (PSI) and conventional surgical instrumentation (CSI) for total knee arthroplasty (TKA) in terms of early implant migration, alignment, surgical resources, patient outcomes, and costs. PATIENTS AND METHODS: The study was a prospective, randomized controlled trial of 50 patients undergoing TKA. There were 25 patients in each of the PSI and CSI groups. There were 12 male patients in the PSI group and seven male patients in the CSI group. The patients had a mean age of 69.0 years (sd 8.4) in the PSI group and 69.4 years (sd 8.4) in the CSI group. All patients received the same TKA implant. Intraoperative surgical resources and any surgical waste generated were recorded. Patients underwent radiostereometric analysis (RSA) studies to measure femoral and tibial component migration over two years. Outcome measures were recorded pre- and postoperatively. Overall costs were calculated for each group. RESULTS: There were no differences (p > 0.05) in any measurement of migration at two years for either the tibial or femoral components. Movement between one and two years was < 0.2 mm, indicating stable fixation. There were no differences in coronal or sagittal alignment between the two groups. The PSI group took a mean 6.1 minutes longer (p = 0.04) and used a mean 3.4 less trays (p < 0.0001). Total waste generated was similar (10 kg) between the two groups. The PSI group cost a mean CAD$1787 more per case (p < 0.01). CONCLUSION: RSA criteria suggest that both groups will have revision rates of approximately 3% at five years. The advantages of PSI were minimal or absent for surgical resources used and waste eliminated, and for meeting target alignment, yet had significantly greater costs. Therefore, we conclude that PSI may not offer any advantage over CSI for routine primary TKA cases. Cite this article: Bone Joint J 2019;101-B:565-572.

Highly crosslinked polyethylene wear rates and acetabular component orientation: a minimum ten-year follow-up.

Aims: The aim of this study was to determine whether there is a difference in the rate of wear between acetabular components positioned within and outside the 'safe zones' of anteversion and inclination angle. Patients and Methods: We reviewed 100 hips in 94 patients who had undergone primary total hip arthroplasty (THA) at least ten years previously. Patients all had the same type of acetabular component with a bearing couple which consisted of a 28 mm cobalt-chromium head on a highly crosslinked polyethylene (HXLPE) liner. A supine radiostereometric analysis (RSA) examination was carried out which acquired anteroposterior (AP) and lateral paired images. Acetabular component anteversion and inclination angles were measured as well as total femoral head penetration, which was divided by the length of implantation to determine the rate of polyethylene wear. Results: The mean anteversion angle was 19.4° (-15.2° to 48°, sd 11.4°), the mean inclination angle 43.4° (27.3° to 60.5°, sd 6.6°), and the mean wear rate 0.055 mm/year (sd 0.060). Exactly half of the hips were positioned inside the 'safe zone'. There was no difference (median difference, 0.012 mm/year; p = 0.091) in the rate of wear between acetabular components located within or outside the 'safe zone'. When compared to acetabular components located inside the 'safe zone', the wear rate was no different for acetabular components that only achieved the target anteversion angle (median difference, 0.012 mm/year; p = 0.138), target inclination angle (median difference, 0.013 mm/year; p = 0.354), or neither target (median difference, 0.012 mm/year; p = 0.322). Conclusion: Placing the acetabular component within or outside the 'safe zone' did not alter the wear rate of HXLPE at long-term follow-up to a level that risked osteolysis. HXLPE appears to be a forgiving bearing material in terms of articular surface wear, but care must still be taken to position the acetabular component correctly so that the implant is stable. Cite this article: Bone Joint J 2018;100-B:891-7.

Knee manipulation under anaesthetic following total knee arthroplasty: a matched cohort design.

The purpose of this study was to compare clinical outcomes of total knee arthroplasty (TKA) after manipulation under anaesthesia (MUA) for post-operative stiffness with a matched cohort of TKA patients who did not requre MUA. In total 72 patients (mean age 59.8 years, 42 to 83) who underwent MUA following TKA were identified from our prospective database and compared with a matched cohort of patients who had undergone TKA without subsequent MUA. Patients were evaluated for range of movement (ROM) and clinical outcome scores (Western Ontario and McMaster Universities Arthritis Index, Short-Form Health Survey, and Knee Society Clinical Rating System) at a mean follow-up of 36.4 months (12 to 120). MUA took place at a mean of nine weeks (5 to 18) after TKA. In patients who required MUA, mean flexion deformity improved from 10° (0° to 25°) to 4.4° (0° to 15°) (p < 0.001), and mean range of flexion improved from 79.8° (65° to 95°) to 116° (80° to 130°) (p < 0.001). There were no statistically significant differences in ROM or functional outcome scores at three months, one year, or two years between those who required MUA and those who did not. There were no complications associated with manipulation. At most recent follow-up, patients requiring MUA achieved equivalent ROM and clinical outcome scores when compared with a matched control group. While other studies have focused on ROM after manipulation, the current study adds to current literature by supplementing this with functional outcome scores.

Taperosis: Does head length affect fretting and corrosion in total hip arthroplasty?

Tribocorrosion at the head-neck taper interface - so-called 'taperosis' - may be a source of metal ions and particulate debris in metal-on-polyethylene total hip arthroplasty (THA). We examined the effect of femoral head length on fretting and corrosion in retrieved head-neck tapers in vivo for a minimum of two years (mean 8.7 years; 2.6 to 15.9). A total of 56 femoral heads ranging from 28 mm to 3 mm to 28 mm + 8 mm, and 17 femoral stems featuring a single taper design were included in the study. Fretting and corrosion were scored in three horizontally oriented concentric zones of each taper by stereomicroscopy. Head length was observed to affect fretting (p = 0.03), with 28 mm + 8 mm femoral heads showing greater total fretting scores than all other head lengths. The central zone of the femoral head bore taper was subject to increased fretting damage (p = 0.01), regardless of head length or stem offset. High-offset femoral stems were associated with greater total fretting of the bore taper (p = 0.04). Increased fretting damage is seen with longer head lengths and high-offset femoral stems, and occurs within a central concentric zone of the femoral head bore taper. Further investigation is required to determine the effect of increased head size, and variations in head-neck taper design.

Revision total hip arthroplasty in patients with extensive proximal femoral bone loss using a fluted tapered modular femoral component.

Revision total hip arthroplasty (THA) is challenging when there is severe loss of bone in the proximal femur. The purpose of this study was to evaluate the clinical and radiographic outcomes of revision THA in patients with severe proximal femoral bone loss treated with a fluted, tapered, modular femoral component. Between January 1998 and December 2004, 92 revision THAs were performed in 92 patients using a single fluted, tapered, modular femoral stem design. Pre-operative diagnoses included aseptic loosening, infection and peri-prosthetic fracture. Bone loss was categorised pre-operatively as Paprosky types III-IV, or Vancouver B3 in patients with a peri-prosthetic fracture. The mean clinical follow-up was 6.4 years (2 to 12). A total of 47 patients had peri-operative complications, 27 of whom required further surgery. However, most of these further operations involved retention of a well-fixed femoral stem, and 88/92 femoral components (97%) remained in situ. Of the four components requiring revision, three were revised for infection and were well fixed at the time of revision; only one (1%) was revised for aseptic loosening. The most common complications were post-operative instability (17 hips, 19%) and intra-operative femoral fracture during insertion of the stem (11 hips, 12%). Diaphyseal stress shielding was noted in 20 hips (22%). There were no fractures of the femoral component. At the final follow-up 78% of patients had minimal or no pain. Revision THA in patients with extensive proximal femoral bone loss using the Link MP fluted, tapered, modular stem led to a high rate of osseointegration of the stem at mid-term follow-up. Cite this article: Bone Joint J 2015; 97-B:312-17.

Outcomes and complications of total hip replacement in super-obese patients.

The purpose of this study was to examine the complications and outcomes of total hip replacement (THR) in super-obese patients (body mass index (BMI) > 50 kg/m(2)) compared with class I obese (BMI 30 to 34.9 kg/m(2)) and normal-weight patients (BMI 18.5 to 24.9 kg/m(2)), as defined by the World Health Organization. A total of 39 THRs were performed in 30 super-obese patients with a mean age of 53 years (31 to 72), who were followed for a mean of 4.2 years (2.0 to 11.7). This group was matched with two cohorts of normal-weight and class I obese patients, each comprising 39 THRs in 39 patients. Statistical analysis was performed to determine differences among these groups with respect to complications and satisfaction based on the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index, the Harris hip score (HHS) and the Short-Form (SF)-12 questionnaire. Super-obese patients experienced significantly longer hospital stays and higher rates of major complications and readmissions than normal-weight and class I obese patients. Although super-obese patients demonstrated reduced pre-operative and post-operative satisfaction scores, there was no significant difference in improvement, or change in the score, with respect to HHS or the WOMAC osteoarthritis index. Super-obese patients obtain similar satisfaction outcomes as class I obese and normal-weight patients with respect to improvement in their scores. However, they experience a significant increase in length of hospital stay and major complication and readmission rates.

Ureteroarterial fistulas after radical pelvic surgery: pathogenesis, diagnosis, and therapeutic modalities.

Ureteroarterial fistulas (UAF) are a rare but potentially life-threatening complication of intra-abdominal malignancy, typically occurring after vascular or pelvic surgery. Patients with a history of radical pelvic surgery, chronic indwelling ureteral stents, and prior pelvic radiation appear to be at increased risk. The predisposing risk factors suggest that gynecological oncologists are the likely specialty to face this problem and should be familiar with the clinical presentation and etiology of UAF. We present two such cases to illustrate these salient points of clinical diagnosis and management.

Human cytomegalovirus (CMV)-specific CD8+ T cell responses are reduced in HIV-infected individuals with a history of CMV disease despite CD4+ T cell recovery.

Cytomegalovirus (CMV)-specific immunity was investigated in human immunodeficiency virus (HIV)-infected individuals. A case-control (1:2) study was performed with cases defined as having a history of CMV end-organ disease (n=15) and controls (n=30) matched by current CD4(+) T cell count. CMV-specific CD8(+) T cells responses were quantified using the high throughput Quantiferon-CMV test (Cellestis, Melbourne, Australia). 40/44 (91%) had a positive Quantiferon-CMV test and the magnitude of response to CMV peptides correlated significantly with response to mitogen (p<0.0001) but not with CD4(+) T cell count at the time of testing, CD4(+) T cell nadir or HIV viral load. Cases had a significantly lower Quantiferon-CMV test than controls but there was no significant difference in response to mitogen or other antigens. In individuals with a history of CMV disease, CMV-specific CD8(+) T cell responses are reduced even in the setting of CD4(+) T cell reconstitution.

Complications following management of displaced intra-articular calcaneal fractures: a prospective randomized trial comparing open reduction internal fixation with nonoperative management.

OBJECTIVE: To report on all complications experienced by patients with displaced intra-articular calcaneal fractures (DIACFs) following nonoperative management or open reduction internal fixation (ORIF). DESIGN: Prospective, randomized, multicenter study. SETTING: Four level I trauma centers. PATIENTS: The patient population consisted of consecutive patients, age 17 to 65 at the time of injury, presenting to 1 of the centers with DIACFs between April 1991 and December 1998. INTERVENTIONS: Patients were randomized to the nonoperative treatment group or to operative reduction using a lateral approach to the calcaneus. MAIN OUTCOME MEASUREMENTS: Follow-up for patients was at 2 weeks, 6 weeks, 3 months, 12 months, 24 months, and once greater than 24 months following injury. At each follow-up interval, patients were assessed for the development of major and minor complications. After a minimum of 2-year follow-up, patients were asked to fill out a validated visual analogue scale questionnaire (VAS) and a general health review (SF-36). RESULTS: There were 226 DIACFs (206 patients) in the ORIF group with 57 of 226 (25%) fractures (57 of 206 patients [28%]) having at least 1 major complication. Of 233 fractures (218 patients) nonoperatively managed, 42 (18%) (42 of 218 patients [19%]) developed at least 1 major complication (indirectly resulting in surgery). CONCLUSION: Complications occur regardless of the management strategy chosen for DIACFs and despite management by experienced surgeons. Complications are a cause of significant morbidity for patients. Outcome scores in this study tend to support ORIF for calcaneal fractures. However, ORIF patients are more likely to develop complications. Certain patient populations (WCB and Sanders type IV) developed a high incidence of complications regardless of the management strategy chosen.

Evaluation of outcomes in patients following surgical treatment of chronic exertional compartment syndrome in the leg.

OBJECTIVE: To evaluate outcomes in patients who had a fasciotomy performed on their leg(s) for chronic exertional compartment syndrome (CECS). DESIGN: A retrospective descriptive cohort study. SETTING: Tertiary care sport medicine referral practice. PATIENTS: A consecutive series of 62 patients surgically treated for CECS from January 1991 to December 1997. MAIN OUTCOME MEASURES: A questionnaire was designed and developed to assess pain (using a 100 mm visual analogue scale), level of improvement, level of maximum activity, satisfaction level, and the occurrence of reoperations. RESULTS: Fifty patients had anterior/lateral compartment involvement, 8 patients had deep posterior compartment involvement, and 4 patients had anterior/lateral/deep posterior compartment involvement. The demographics of the 39 respondents and 23 nonrespondents were similar. The mean percent pain relief of respondents was 68% (95% CI [confidence interval] = 54% to 82%). There was no relationship between percent pain relief and the documented immediate post exercise compartment pressures. A clinically significant improvement was reported by 26 of 32 (81%) anterior/lateral compartment patients and 3 of 6 (50%) patients with deep posterior compartment involvement. Patient level of activity after fasciotomy was classified as equal to or higher than before the operation with a lesser degree of pain by 28 of 36 (78%) patients, while 8 of 36 (22%) patients reported lower activity levels than before the operation. Of the patients reporting lower activity, seven were due to exercise related pain in the post operative leg(s) and one was due to lifestyle changes. Thirty of 38 patients (79%) were satisfied with the outcome of the operation. Four of 62 patients (6%) failed the initial surgical procedure and required revision surgery for exercise-induced pain. In addition, one of these individuals also had a sympathectomy and another had a neurolysis performed at the time of revision surgery. Three of the 62 (5%) patients had subsequent operations for exercise-induced pain on different compartments than the initial surgical procedure. One individual had an unsuccessful operative repair of a posttraumatic neuroma. Postoperative complications were reported by 5 of 39 (13%) patients in the additional comments section of the questionnaire. CONCLUSIONS: The majority of patients surgically treated for CECS experience a high level of pain relief and are satisfied with the results of their operation. The level of pain relief experienced by patients is not related to the magnitude of the immediate post exercise compartment pressures. Despite the possibility that some patients have less favorable outcomes, experience complications, or need subsequent operations, fasciotomy is recommended for patients with CECS as there is no other treatment for this condition.

An audit of the effect of intravenous antibiotic treatment on spirometric measures of pulmonary function in cystic fibrosis.

BACKGROUND: This retrospective audit was undertaken to compare the efficacy of home intravenous (i.v.) antibiotic therapy, hospital i.v. antibiotic therapy and a combination of these 2 approaches, as determined by spirometric measures of lung function in cystic fibrosis (CF) patients, each with an acute respiratory exacerbation. METHODS: Pulmonary function, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow rate between 25 per cent and 75 per cent of vital capacity (FEF25-75), and peak expiratory flow rate (PEFR) were compared between groups at the beginning and at the end of an IV antibiotic course. RESULTS: Treatment of exacerbations resulted in a significant improvement (p < 0.05) in lung function irrespective of where patients were treated. The percentage improvement in FEV1, FVC, and FEF25-75, were significantly greater in patients treated in hospital compared to those who had home i.v. treatment (p < 0.05). CONCLUSION: Hospital i.v. antibiotic therapy resulted in greater improvements in FEV1, FVC and FEF25-75 than home i.v. antibiotic therapy in CF patients with an acute respiratory infection.

Diminished production of human immunodeficiency virus type 1 in astrocytes results from inefficient translation of gag, env, and nef mRNAs despite efficient expression of Tat and Rev.

Astrocytes infected with human immunodeficiency virus type 1 (HIV-1) produce only minimal quantities of virus. The molecular events that limit acute-phase HIV-1 infection of astrocytes were examined after inducing acute-phase replication by transfection with the pNL4-3 proviral plasmid. The levels of HIV-1 mRNA were similarly high in both astrocytes and HeLa cells, but astrocytes produced approximately 50-fold less supernatant p24 than HeLa cells. We found that diminished HIV-1 production in astrocytes resulted from inefficient translation of gag, env, and nef mRNAs that were efficiently transported to the cytoplasm. Tat- or Rev-dependent reporter constructs showed no defect in Tat or Rev function in astrocytes compared with HeLa cells. HIV-1 mRNAs were correctly spliced, but only Rev and Tat proteins were efficiently translated from their native mRNAs. Pulse-chase labelling and immunoblot experiments revealed no defect in protein processing, but levels of Gag, Env, or Nef protein expressed were dramatically reduced in astrocytes compared to HeLa cells. These results demonstrate that inefficient translation of HIV-1 structural proteins underlies the restricted infection of astrocytes. The efficient expression of functional Tat and Rev by astrocytes may contribute to HIV-1 neuropathogenesis.

Sequential extraction analysis of heavy metals in sediments of variable composition using nitrilotriacetic acid to counteract resorption.

Artificial sediments were made that contained variable amounts (up to 20% by weight) of feldspar, calcite, Fe-oxide or organic matter. Analysis of samples spiked with Pb and Zn in the presence and absence of nitrilotriacetic acid (NTA) showed that 400 mg l(-1) of chelating agent greatly reduced or eliminated sorption in each case. Further study showed that this NTA concentration did not cause significant mineral dissolution. Resorption during sequential extraction analysis of artificial sediments is indicated by the fact that with NTA, levels of metals are higher in the first step and lower during subsequent steps, compared with levels obtained without NTA. However, the addition of 400 mg l(-1) of NTA to each extracting solution in the sequence appears to be effective for counteracting resorption in feldspathic, calcareous, ferruginous and carbonaceous sediments.

Jurors rate RNs. Counting the costs.

To gain a perspective on how the public views nurses' legal accountability, a group of jurors was surveyed. This study examines the conditions that RNs face, as well as their liability under these conditions.

1192U90 in animal tests that predict antipsychotic efficacy, anxiolysis, and extrapyramidal side effects.

1192U90 was developed on the assumption that antagonism of 5-HT2 receptors efficacy yields more potently than D2 receptors against positive and negative symptoms of schizophrenia with minimal liability for extrapyramidal side effects (EPSs), and that 5-HT1A agonism further reduces EPSs and provides anxiolytic and antidepressant activity. 1192U90 was submitted to four tests that predict antipsychotic efficacy (antagonism of apomorphine-induced climbing in mouse, antagonism of apomorphine-induced circling in rats with unilateral 6-OHDA lesions, antagonism of amphetamine-induced hyperlocomotion in rat, and inhibition of conditioned avoidance in rat), two tests of 5-HT2 function (antagonism of 5-MeODMT-induced head twitches in mouse and antagonism of 5-HTP-induced wet dog shakes in rat), and three tests that predict EPS liability (antagonism of apomorphine-induced stereotypy in mouse and rat and induction of catalepsy in mouse). ED50s (mg/kg PO) were as follows: climbing 10.1, circling 7.9, hyperlocomotion 6.6, and avoidance 5.7; head twitches 5 and wet dog shakes 4.6; stereotypy in mouse 91.1, stereotypy in rat 133.4, and catalepsy 192.4. The ratio of ED50 for stereotypy antagonism to ED50 for climbing antagonism was 9 (compared to 4, 3, and 4 for clozapine, risperidone, and haloperidol). The ratio of ED50 for catalepsy induction to ED50 for climbing antagonism was 19 (compared to 7, 2, and 17 for clozapine, risperidone, and haloperidol). 1192U90 was also submitted to three tests that predict anxiolysis: It produced only a small increase in punished lever pressing for food in rat (Geller-Seifter conflict test), which is specific for rapid-onset efficacy, but produced large increases in punished key pecking for food in pigeon and cork gnawing in rat, which identify the delayed onset 5-HT1A agonists such as buspirone. The results suggest that 1192U90 would be effective for positive and negative symptoms of schizophrenia, with minimal liability for EPSs, and may also have anxiolytic properties.

Sequential extraction analysis of heavy metals using a chelating agent (NTA) to counteract resorption.

The geochemical partitioning of Pb, Ni and Zn in contaminated quartz-rich sediment and soil samples was characterized by sequential extraction analysis in the presence and absence of nitrilotriacetic acid (NTA). With NTA, levels of metals recovered are higher in the earlier steps and lower in the later steps of the procedure. This suggests that post-extraction resorption is effectively counteracted by chelation, thereby improving the accuracy of the method. An NTA concentration of 200 mg liter(-1) appears to be sufficient for counteracting resorption without causing significant dissolution of non-targeted phases in the samples studied. However, experiments using reference materials spiked with solutions containing Pb, Ni, Cu and Zn suggest that resorption will remain a problem when large amounts of strong sorbents such as organic matter are present. The results also show that although post-extraction resorption does occur in the absence of NTA, the magnitude of resorption is small (<20 to 30% of the summed total of metal present in the sample) in quartz-rich sediments.

The medical costs attributable to meat consumption.

OBJECTIVE: To estimate the medical costs that are attributable to the health effects of meat consumption. METHODS: The prevalence of hypertension, heart disease, cancer, diabetes, gallstones, obesity, and foodborne illness among omnivores and vegetarians are compared in studies that have controlled for other lifestyle factors, and the corresponding attributable medical costs are calculated in 1992 dollars. RESULTS: Direct health care costs attributable to meat consumption are estimated to be +2.8-8.5 billion for hypertension, +9.5 billion for heart disease, +0-16.5 billion for cancer, +14.0-17.1 billion for diabetes, +0.2-2.4 billion for gallbladder disease, +1.9 billion for obesity-related musculoskeletal disorders, and +0.2-5.5 billion for foodborne illness. The total direct medical costs attributable to meat consumption for 1992 are estimated at +28.6-61.4 billion. CONCLUSION: Health care costs attributable to meat consumption are quantifiable and substantial.

Health effects of water restriction to motivate lever-pressing in rats.

The objectives were to determine the degree of water restriction necessary and sufficient to motivate operant behavior in rat and the physiologic and general health effects of chronic daily water restriction. Ovariectomized Long-Evans rats were deprived of water for 21, 14, or 7 h per day and allowed to press a lever to earn a drop of water. The 21-h group acquired the response, but the 14-h and 7-h groups did not. Once the response was acquired, all three restriction levels supported lever pressing, but the lower levels supported lower rates. After 3 months on the restriction schedules, there were no differences from similarly restricted nonbehavioral subjects or ad-libitum controls in growth rate (except for early transient weight loss), appearance of organs and tissues at gross necropsy, hematologic examination, or clinical chemical analysis. The results demonstrate the necessity and safety of the 21-h restriction schedule for behavioral work.

T cell receptor antagonist peptides induce positive selection.

We have used organ culture of fetal thymic lobes from T cell receptor (TCR) transgenic beta 2M(-/-) mice to study the role of peptides in positive selection. The TCR used was from a CD8+ T cell specific for ovalbumin 257-264 in the context of Kb. Several peptides with the ability to induce positive selection were identified. These peptide-selected thymocytes have the same phenotype as mature CD8+ T cells and can respond to antigen. Those peptides with the ability to induce positive selection were all variants of the antigenic peptide and were identified as TCR antagonist peptides for this receptor. One peptide tested, E1, induced positive selection on the beta 2M(-/-) background but negative selection on the beta 2M(+/-) background. These results show that the process of positive selection is exquisitely peptide specific and sensitive to extremely low ligand density and support the notion that low efficacy ligands mediate positive selection.

A novel, potent and selective nonpeptidic delta opioid receptor agonist BW373U86.

Four different opioid receptor binding assays and three different isolated tissue studies were used to screen for delta receptor-selective nonpeptidic compounds. (+/-)-4-((alpha-R*)-alpha-((2S*,5R*)-4-Allyl-2,5- dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (BW373U86) was a potent delta receptor-selective ligand in receptor binding assays. The Ki values were 1.8 +/- 0.4, 15 +/- 3, 85 +/- 4 and 34 +/- 3 nM for delta, mu, epsilon and kappa receptor binding sites, respectively. BW373U86 inhibited electrically evoked muscle contraction of mouse vas deferens with an ED50 value of 0.2 +/- 0.06 nM. This inhibitory effect of BW373U86 was antagonized by the delta receptor-selective antagonist naltrindole in a competitive manner: the Schild plot indicated a slope of 1 and a pA2 value of 9.43 (Ke = 3.7 x 10(-10) M), which is consistent with the high affinity of naltrindole in delta receptors. BW373U86 did not interact significantly with other receptors. BW373U86 inhibited the acoustic startle reflex after subcutaneous administration from 0.2- to 2-mg/kg doses in rats, and this inhibition was blocked by naltrindole. BW373U86 also induced a dose-dependent increase of locomotor activity in rats at similar doses. This effect was inhibited by naltrindole. These data suggest that BW373U86 is a potent and selective nonpeptidic delta agonist, and it elicits distinct in vivo pharmacological activities.