Proteomics Profiling of Human Synovial Fluid Suggests Increased Protein Interplay in Early-Osteoarthritis (OA) That Is Lost in Late-Stage OA.

The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear), and from deceased controls without knee OA. Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e., interplay) between the proteins in each group. More proteins were increased in early-OA versus controls than late-stage OA versus controls. For most of these proteins, the fold changes between late-stage OA versus controls and early-stage OA versus controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time, this study illustrated distinct patterns in protein co-expression suggesting that the interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should focus on earlier stages of the disease than previously considered.

Higher aggrecan 1-F21 epitope concentration in synovial fluid early after anterior cruciate ligament injury is associated with worse knee cartilage quality assessed by gadolinium enhanced magnetic resonance imaging 20 years later.

BACKGROUND: To investigate if cartilage related biomarkers in synovial fluid are associated with knee cartilage status 20 years after an anterior cruciate ligament (ACL) injury. METHODS: We studied 25 patients with a complete ACL rupture without subsequent ACL reconstruction or radiographic knee OA. All had a delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) 20 years after the ACL injury, using the T1 transverse relaxation time in the presence of gadolinium (T1Gd) which estimates the concentration of glycosaminoglycans in hyaline cartilage. Synovial fluid samples were aspirated acutely (between 0 and 18 days) and during 1 to 5 follow up visits between 0.5 and 7.5 years after injury. We quantified synovial fluid concentrations of aggrecan (epitopes 1-F21 and ARGS), cartilage oligomeric matrix protein, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by immunoassays, and sulfated glycosaminoglycans by Alcian blue precipitation. Western blot was used for qualitative analyses of aggrecan fragments in synovial fluid and cartilage samples. RESULTS: Western blot indicated that the 1-F21 epitope was located within the chondroitin sulfate 2 region of aggrecan. Linear regression analyses (adjusted for age, sex, body mass index and time between injury and sampling) showed that acute higher synovial fluid 1-F21-aggrecan concentrations were associated with shorter T1Gd values 20 years after injury, i.e. inferior cartilage quality (standardized effects between - 0.67 and - 1.0). No other statistically significant association was found between molecular biomarkers and T1Gd values. CONCLUSION: Higher acute synovial fluid 1-F21-aggrecan concentrations in ACL injured patients, who managed to cope without ACL reconstruction and were without radiographic knee OA, were associated with inferior knee cartilage quality assessed by dGEMRIC 20 years after injury.

Poor outcome after a surgically treated chondral injury on the medial femoral condyle: early evaluation with dGEMRIC and 17-year radiographic and clinical follow-up in 16 knees.

Background and purpose - The optimal treatment for traumatic cartilage injuries remains unknown. Contrast-enhanced MRI of cartilage (dGEMRIC) evaluates cartilage quality and a low dGEMRIC index may predict radiographic osteoarthritis (OA). The purpose of this study was (a) to explore the results 17 years after surgical treatment of an isolated cartilage knee injury and (b) to evaluate the predictive value of dGEMRIC. Patients and methods - 16 knees with an isolated traumatic cartilage injury of the medial femoral condyle had cartilage repair surgery either by microfracture or autologous cartilage implantation. dGEMRIC of the injured knee was performed 2 years after surgery and radiographic examinations were performed 17 years after the operation. Results - Radiographic OA was present in 12 of 16 knees. Irrespective of surgical method, the dGEMRIC index was lower in repair tissue compared with adjacent cartilage in the medial compartment, 237 ms vs. 312 ms (p < 0.001), which in turn had lower value than in the non-injured lateral cartilage, 312 ms vs. 354 ms (p < 0.008). The dGEMRIC index in the cartilage adjacent to the repair tissue correlated negatively with radiographic osteophyte score, r = -0.75 (p = 0.03). Interpretation - A traumatic cartilage injury is associated with a high prevalence of OA after 17 years. The low dGEMRIC index in the repair tissue 2 years postoperatively indicates fibrocartilage of low quality. The negative correlation between the dGEMRIC index in the adjacent cartilage and future OA suggests that the quality of the surrounding cartilage influences outcome after cartilage repair surgery.

Knee arthroscopies: who gets them, what does the radiologist report, and what does the surgeon find? An evaluation from southern Sweden.

BACKGROUND AND PURPOSE: Several randomized controlled trials have not shown any added benefit of arthroscopy over placebo surgery or physiotherapy in middle-aged patients with knee symptoms without trauma. We studied the characteristics of the knee arthroscopies performed in southern Sweden. PATIENTS AND METHODS: From the orthopedic surgical records from 2007-2009 in the Skåne region of Sweden (with a population of 1.2 million), we retrieved ICD-10 diagnostic codes and selected all 4,096 arthroscopies that were diagnosed peroperatively with code M23.2 (derangement of meniscus due to old tear or injury) or code M17 (knee osteoarthritis). We extracted information on cartilage and meniscus status at arthroscopy, and we also randomly sampled 502 of these patients from the regional archive of radiology and analyzed the preoperative prevalence of radiographic or magnetic resonance imaging (MRI)-defined osteoarthritis. RESULTS: 2,165 (53%) of the 4,096 arthroscopies had the diagnostic code M23.2 or M17. In this subgroup, 1,375 cases (64%) had typical findings consistent with degenerative meniscal tear (i.e. that correspond to a degenerative meniscal tear in at least a third of all arthroscopies). Of the randomly sampled patients, the preoperative prevalence of radiological knee osteoarthritis was 46%. INTERPRETATION: There is a discrepancy between evidence-based medicine treatment guidelines and clinical practice regarding the amount of knee arthroscopies performed in patients with symptoms of degenerative knee disease.

Outcomes >30 Years After Initial Nonoperative Treatment of Anterior Cruciate Ligament Injuries.

BACKGROUND: It is unclear how anterior cruciate ligament (ACL) reconstruction (ACLR) affects the development of osteoarthritis (OA). This uncertainty is partly caused by the lack of long-term studies on ACL injuries treated primarily without reconstruction and the underreporting of symptomatic OA. PURPOSE: To determine (1) the knee function, symptoms, and activity level, as well as the presence of radiographic and symptomatic OA; (2) how these clinical outcomes have changed over time; and (3) the frequency of subsequent knee surgeries after the index ACL injury in a cohort of patients with ACL injuries treated primarily without reconstruction. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 100 patients underwent initial nonoperative treatment >30 years ago (mean, 33.2 ± 1.4 years). Of these, 81 patients (mean age, 59 ± 8 years) completed the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Scoring Scale, and Tegner Activity Scale. Seventy-three patients underwent radiography to evaluate tibiofemoral and patellofemoral OA in the ACL-injured knee. Patients only underwent late ACLR if they experienced insufficient knee stability. RESULTS: At 33 years after the ACL injury, the KOOS Activities of Daily Living subscore was better than population-based reference values, but scores were similar for the remaining KOOS subscales. Furthermore, 65% of patients had a good or excellent Lysholm score (≥84 points). The Tegner score decreased 4 points from before the injury to 33-year follow-up (P < .001). Most patients (75%) had evidence of radiographic tibiofemoral and/or patellofemoral OA, but only 38% were classified as having symptomatic OA (defined as radiographic OA in combination with a symptomatic knee according to cutoffs on the KOOS). Approximately 50% underwent meniscal surgery, and 29% subsequently underwent ACLR for recurrent instability. There were 2 patients who underwent total knee replacement. CONCLUSION: Despite a high prevalence of radiographic OA, patients achieved acceptable subjective knee function and had a relatively low prevalence of symptomatic OA at >30 years after an ACL injury when an initial nonoperative treatment strategy was employed.

Sick leave after arthroscopic meniscus repair vs. arthroscopic partial meniscectomy.

Objective: To evaluate sick leave after meniscal repair vs arthroscopic partial meniscectomy (APM) and, for comparison, vs the general population. Method: Using Swedish register data we included all employed persons aged 19-49 years in the general population of Skåne region and identified those having had meniscus repair or APM in the period of 2005-2012. We retrieved data on sick leave during 1 year before until 2 years after surgery. We used logistic regression to estimate the risk differences of being on sick leave and negative binomial model to analyze differences in the number of days on sick leave. Results: We included 192 persons with meniscus repair, 2481 with APM, and 376 â€‹345 references without meniscus surgery. Of these, 55% of meniscus repair group, 43% of APM group had any sick leave in the 2-year period following the surgery, while 17% of the references were on sick leave in the corresponding period. The mean (SD) number of days of sick leave after meniscus repair was 55 (77) days and for APM 37 (86) days. Meniscus repair was associated with higher probability of sick leave compared to APM with an adjusted risk difference of 0.13 (95% CI 0.07-0.19). Conclusion: Persons undergoing meniscus repair have more frequent and 37% longer periods of sick leave in the short term than persons undergoing APM. However, sick leave in the long-term warrant further attention as successful repair may be associated with less knee osteoarthritis development than APM.

Patient's subjective knee function 3-5 years following partial meniscectomy or meniscus repair compared to a normal population: a retrospective cohort study.

Purpose: Evaluate patient-reported knee function after arthroscopic partial meniscectomy (APM) and meniscus suture repair in two different age cohorts compared with a normal population. Method: Arthroscopic meniscus surgery was performed on 421 patients at Skåne University Hospital from 2010 to 2014, with a mean (SD) follow-up of 4.2 (1.4) years. Patients and controls were divided into two age cohorts; 18-34 years (younger) and 35-54 years (middle-aged) as well as according to surgery performed; either solely meniscus surgery or with concurrent anterior cruciate ligament reconstruction (ACLR). The outcome is measured with the five subscales of the Knee and Osteoarthritis Outcome Score (KOOS). Results: No significant difference in outcome after all studied types of meniscus surgeries between younger-aged and middle-aged patients.Younger patients with APM or meniscus suture repair, with or without, ACLR score lower than the normal population in all subscales of KOOS (p<0.001), except in Activities of Daily Living (ADL) for meniscus suture patients.Middle-aged patients with APM score lower in all subscales than the normal population (p≤0.009). Those with meniscus suture repair score lower than the normal population only for the subscales Sport/Rec and quality of life (p<0.001).Both younger-aged and middle-aged patients achieve better KOOS values after meniscus suture repair and ACLR than after all other combinations of surgery. Conclusion: Patients with meniscus injuries do not reach the same KOOS score as the normal population, irrespective of age or type of meniscus surgery performed. However, combined with ACLR in younger-aged and middle-aged patients, meniscus suture gives a better subjective outcome than isolated meniscus surgery.

The effect of pre-exposure and recovery type on activity-based anorexia in rats.

Activity-based anorexia (ABA) occurs when there is limited access to food and an opportunity to engage in high levels of physical activity. While the ABA effect is well established, the distinct functions of exercise and food restriction in maintaining ABA have not been determined. The current study examined the effect of pre-exposure to a restricted feeding schedule and pre-exposure to a running wheel on the incidence of ABA in 36 rats. Access to food and the running wheel was also varied in the recovery phase of the study in order to establish the effect of these variables on recovery from ABA. Three adaptation conditions (pre-exposed to food restriction, pre-exposed to wheel access and non-exposed) and two recovery conditions (wheel access and food restriction recovery) defined the six groups in the current study. Pre-exposure to food restriction was found to ameliorate the ABA effect during the anorexia phase while pre-exposure to wheel access exacerbated ABA. It was also found that subjects in the wheel access recovery condition gained more weight than the subjects in the food restriction recovery. In food restriction recovery, there was an interaction between the adaptation and recovery condition, with subjects that were pre-exposed to food restriction gaining the most weight. The results of the current study aid in understanding the distinct functions of food restriction and exercise in maintaining and recovering from ABA and have possible implications for the treatment of people diagnosed with some types of anorexia nervosa.

The influence of posterior-inferior tibial slope in ACL injury.

PURPOSE: To explore the effect of different posterior-inferior tibial slope (PITS) angles on ACL injury at non-contact sports, knee laxity and the need for ACL reconstruction. METHODS: One hundred patients with an acute, arthroscopically verified total ACL rupture were followed prospectively with the intention of treating the injury without reconstruction. Knee laxity was assessed with the Lachman and pivot shift tests with the patients under general anesthesia within 10 days of injury. After 15 years, 22 patients of 94 available for follow-up had undergone reconstruction a mean of 4 years after injury. Reconstruction was performed in case of repeated giving-way episodes (n = 16) or meniscus lesions suitable for fixation (n = 6). Knee radiographs were available from 82 patients. Two independent readers determined the PITS angle. RESULTS: Patients injured in contact sports had a greater mean PITS angle than those injured in non-contact sports (10.5° and 9.3°, respectively, P = 0.03). The mean PITS angle was 10.1 (SD = 2.3) for non-reconstructed knees and 9.1 (SD = 3.0) for reconstructed knees (P = NS). Eight of 17 reconstructed knees showed a PITS angle of less than 7.6° (P = 0.006), and the odds ratio of need for reconstruction was 3.9 (CI 1.26-12.3, P = 0.02). No significant difference in PITS angle was found between patients with low- and high-grade instability. CONCLUSION: The main finding of the study was that reconstructed knees were overrepresented in knees with extremely low PITS angles. Additionally, patients injured in contact sports had higher PITS angles than those injured in non-contact sports, and PITS angle did not influence knee laxity.

Repeatability of T1-quantification in dGEMRIC for three different acquisition techniques: two-dimensional inversion recovery, three-dimensional look locker, and three-dimensional variable flip angle.

PURPOSE: To evaluate the repeatability of the dGEMRIC (delayed gadolinium enhanced MRI of cartilage) method in osteoarthritis-prone knee joints for three different T1 quantification techniques: two-dimensional inversion recovery (2D-IR), three-dimensional Look-Locker (3D-LL), and three-dimensional variable flip angle (3D-VFA). MATERIALS AND METHODS: Nine subjects were examined twice, with a 2-week interval, using all three measurement techniques. Four regions of interest were defined in the central medial and lateral femoral cartilage. The repeatability was evaluated for each measurement technique. For the 3D techniques, the variation between different slices was also evaluated. RESULTS: Repeatability expressed by root-mean-square coefficient of variation (CV(RMS)) showed similar results for 2D-IR and 3D-LL (5.4-8.4%). For 3D-VFA CV(RMS) was higher (9.3-15.2%). Intraclass correlation coefficient showed both 2D-IR and 3D-LL reliability to be moderate, while 3D-VFA reliability was low. Inter-slice CV(RMS) and ICC was of the same magnitude as the repeatability. No clear differences could be interpreted between the condyles. CONCLUSION: Both 2D-IR and 3D-LL perform well in generating repeatable dGEMRIC results, while 3D-VFA results are somewhat inferior. Furthermore, repeatability results in this study are similar to previously published results for healthy subjects. Finally, the positioning of the analyzed images is crucial to generate reliable repeatability results.

Sick leave before and after arthroscopic partial meniscectomy due to traumatic meniscal tear.

Objective: There is limited knowledge on sick leave associated with arthroscopic partial meniscectomy (APM) due to traumatic meniscal tear and its potential gender differences. Thus, our aim was to determine gender-specific sick leave before and after APM. Method: In Skåne region, Sweden, we identified patients, aged 18-59 years diagnosed with traumatic meniscal tear without ligament injury, who had APM during 2004-2012. For each patient, we randomly sampled four age- and sex-matched reference subjects from the general population. We retrieved social insurance register data of all-cause sick leave exceeding two weeks. We analyzed the proportions and duration of sick leave with respect to days of sick leave, age, and gender. Results: The cohort comprised 604 patients (29% women), mean (SD) age 40 (11) years, and 2254 reference subjects. Thirty-nine percent of women and 27% of men had a sick leave period longer than 14 days after APM. Still, we found that a new period of sick leave longer than 14 days, initiated on the day of APM (and not before), was relatively uncommon and equally distributed (15%) between women and men. Conclusion: About one-third of the patients have more than 2 weeks of sick leave after APM for a traumatic meniscal tear and women are overrepresented in this category. Prolonged sick leave initiated on the day of APM was relatively uncommon. Other factors than surgery seem to explain the prolonged sick leave.

Free radical damage as a biomarker of bladder dysfunction after partial outlet obstruction and reversal.

OBJECTIVE: To investigate the use of free-radical generation as a result of protein carbonylation and nitrotyrosination to characterize the level of bladder dysfunction after partial bladder outlet obstruction (PBOO) and reversal. MATERIALS AND METHODS: We surgically created PBOO in male New Zealand White rabbits; after 4 weeks of PBOO, one group of six rabbits was assessed, while the PBOO was relieved in two additional groups of six rabbits each that were assessed at 4 and 8 weeks after relieving the PBOO. Six sham-operated rabbits served as controls. Sedated rabbits were assessed by cystometry and the bladders were then removed for contractile, histological and molecular studies. Western blotting was used to determine the level of carbonylation and nitrotyrosination at the protein level. RESULTS: The PBOO group had significant decreases in the contractile responses to field stimulation, ATP, carbachol and KCl. The responses to all forms of stimulation increased significantly at 4 weeks after reversal, and further increased to near normal levels by 8 weeks. Similarly, compliance and cystometric values also returned to near normal values after reversal. The hypertrophied smooth muscle of the obstructed bladders regressed to near-normal size. There was a significant increase in the level of carbonylation and nitrotyrosination after PBOO, and a progressive decrease in the 4-week reversal groups, nearing control values by 8 weeks. CONCLUSIONS: Significantly increased carbonylation and nitrotyrosination levels after PBOO correlated with the severe dysfunction in the obstructed rabbits. Similarly, decreased levels of oxidation and nitration correlated with the functional recovery after reversal.

Changes in the smooth muscle of the corpora cavernosum related to reversal of partial bladder outlet obstruction in rabbits.

Previous studies have demonstrated that partial bladder outlet obstruction (PBOO) in the rabbit induces an increase in corpus cavernosum smooth muscle (CCSM) tone, which may make it difficult for the CCSM to relax. Thus, to determine whether the corpus cavernosum restores relaxation after reversal of PBOO, we investigated the physiologic, histologic, and cell biology in penises obtained from rabbits 4 weeks and 8 weeks after reversal of PBOO. CCSM from bladder outlet-obstructed and obstruction-reversed rabbits showed significant decreases in the contractile responses to phenylephrine. The relaxation responses to electrical field stimulation (EFS), ATP, acetylcholine, and sodium nitroprusside (SNP) were decreased in obstructed and reversed for 4 weeks groups. By 8 weeks of reversal, the relaxation of CCSM was increased gradually in response to EFS, SNP, and acetylcholine. However, the response to ATP did not result in the relaxation of CCSM to control levels. The ratio of SM to collagen decreased after obstruction and remained low after reversal. Expression of both isoforms of Rho kinase (ROK) was increased in obstruction groups. At 4 weeks of reversal, the expression of ROK alpha remained at obstruction level, whereas ROK beta expression decreased in comparison with the obstruction group. By 8 weeks of reversal, expression of both ROK alpha and beta significantly decreased when compared with the obstruction group. These results suggested that the poor relaxation response at reversal of 4 weeks was associated with incomplete decreased expression of both isoforms of ROK, whereas the incomplete recovery of the CCSM relaxation response at reversal of 8 weeks may be associated with structural alterations in the CC and irreversible damage from PBOO.

The effect of chronic partial bladder outlet obstruction on corpus cavernosum smooth muscle and Rho-kinase in rabbits.

AIM: The goal of this study was to investigate the effect of different severities in bladder dysfunction on corpus cavernosum physiology, morphology and expression of Rho-kinase in rabbits. METHODS: Male New Zealand rabbits were divided into control, 2 and 8 weeks of partial bladder outlet obstruction (PBOO) groups. Isolated cavernosal strips from all groups were precontracted with phenylephrine and the relaxant responses to electrical field stimulation (EFS), ATP, acetylcholine, and sodium nitroprusside (SNP) were determined. Histological and molecular studies were performed. RESULTS: Corpus cavernosum smooth muscle (CCSM) from 8 weeks obstruction rabbits showed significant decreases in the contractile response to phenylephrine and further decreased relaxation responses to EFS in comparison to 2 weeks group. Relaxation induced by ATP, acetylcholine, and SNP were all significantly diminished at both 2 and 8 weeks obstruction equally. The ratio of smooth muscle to collagen decreased at 2 weeks and further dropped at 8 weeks obstruction. Expression of both isoforms of Rho-kinase were increased in both obstruction groups at 2 weeks obstruction and decreased significantly (from the 2 week obstructed values) at 8 weeks while remaining above control values. CONCLUSION: The present study indicated that severe bladder dysfunction secondary to chronic PBOO induced significant physiological dysfunctions of CCSM as well as morphological changes. Activities of both ROK isoenzymes showed increases at 2- and 8-week obstructions. Increase in Rho-kinase expression/activity would be expected to make the CCSM more difficult to relax and also contribute to reduction of EFS-induced relaxation of CCSM after chronic PBOO.

Vernacular Selection: What to Say and When to Say It.

The language of behavior analysis is precise in the sense that it focuses attention on functional relations between behavior and the environment that are extended in time. However, to non-behavior analysts, behavior-analytic terms and explanations are difficult to understand and awkward sounding. Evidence suggests that this has had deleterious effects on the acceptance of the field of behavior analysis and its explanations of behavior. The goal of this article is to assert that verbal behavior that describes behavior is functionally related to subsequent explanatory verbal behavior. In addition, it is argued that technical language is not a requirement of precision and logical formulation. Suggestions are made regarding how behavior analysts can generate evidence to better understand explanatory preferences of individuals with various amounts of exposure to behavior analysis. In addition, methods are suggested for introducing behavior analysis to others with vernacular descriptions of behavior and its causes that do not obscure critical distinctions by introducing mental/mediational explanations.

Activity level and subjective knee function 15 years after anterior cruciate ligament injury: a prospective, longitudinal study of nonreconstructed patients.

BACKGROUND: The activity level and subjective knee function after an anterior cruciate ligament (ACL) injury treated without reconstruction have not been well elucidated. HYPOTHESIS: Patients with ACL injury can achieve good knee function and satisfactory long-term activity level when treated by early activity modification combined with rehabilitation. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. MATERIALS AND METHODS: One hundred patients with an acute total ACL injury were observed for 15 years. All patients initially underwent arthroscopic surgery and a rehabilitation program. They were advised to modify their activity level, especially by avoiding contact sports. Patients with recurrent giving-way episodes and/or secondary meniscal injuries that required fixation (n = 6) were subsequently excluded and underwent reconstruction (n = 22). Sixty-seven patients with unilateral nonreconstructed ACL injury remained at the 15-year follow-up. The Lysholm knee score, Tegner activity level, and a visual analog score for global knee function were recorded at regular intervals. At the final follow-up, patients were further evaluated with the Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) subjective knee evaluation form. RESULTS: Forty patients resumed their preinjury activity level or higher within 3 years. The median activity level 15 years after injury had decreased from 7 to 4 according to Tegner activity scale (P < .001). The mean Lysholm knee score was 96 and 95, 1 and 3 years after injury, respectively, but declined to 86 after 15 years (P < .001). Forty-nine patients had good/excellent results, and 14 had fair (n = 6) or poor function (n = 8) at 15 years. Patients injured in contact sports scored lower in the quality of life sub-scale of KOOS than those injured in noncontact sports (P < .05). Thirteen of the 67 patients (19%) were reoperated with an arthroscopic procedure because of knee symptoms. CONCLUSION: Early activity modification and neuromuscular rehabilitation resulted in a good knee function and an acceptable activity level in the majority of the nonreconstructed patients. The decline in activity level of patients engaged in contact sports at the time of injury affected their subjective quality of life more than patients involved in noncontact sports.

Some comments on the distinction between intention and intentionality.

The topic of intention has recently received attention from behavior analysts (Hineline, 2003; Neuman, 2004). From a behavior-analytic perspective, it is important to identify the circumstances in which people utter such terms, and to identify the potential circumstances that maintain such utterances. It follows that from a behavior-analytic perspective, the focus is primarily on those who observe behavior and attribute intentions to that behavior. However, there has not been a distinction between intention and intentionality. The current analysis stresses the distinction between the two terms, both from a traditional point of view (psychologist and layperson) and from a behavior-analytic point of view. From a behavior analyst's perspective, the distinction is important because observers may be responding to distinct functional relations when they attribute intention or intentionality to behavior.

An intentional interpretive perspective.

To the extent that the concept of intention has been addressed within behavior analysis, descriptions of intention have been general and have not specifically included important distinctions that differentiate a behavior-analytic approach from vernacular definitions of intention. A fundamental difference between a behavior-analytic approach and most other psychological approaches is that other approaches focus on the necessity of intentions to explain behavior, whereas a behavior-analytic approach is directed at understanding the interplay between behavior and environment. Behavior-analytic interpretations include the relations between the observer's behavior and the environment. From a behavior-analytic perspective, an analysis of the observer's interpretations of an individual's behavior is inherent in the subsequent attribution of intention. The present agenda is to provide a behavior-analytic account of attributing intention that identifies the establishing conditions for speaking of intention. Also addressed is the extent to which we speak of intentions when the observed individual's behavior is contingency shaped or under instructional control.

Effect of age on the role of Rho-kinase in short-term partial bladder outlet obstruction.

OBJECTIVES: We examined the expression of Rho-kinase (ROK) isoforms in young and old rabbits' detrusor smooth muscles (SM) during the progression of short-term partial bladder outlet obstruction and correlated them with the time course of obstruction. METHODS: We obtained detrusor samples from bladders after 1, 3, 7, and 14 days of obstruction and also sham-operated control rabbits. We used reverse transcriptase-polymerase chain reaction, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western blotting to determine the relative levels of ROK isoform expression at the mRNA and protein levels. RESULTS: Bladder weight for young rabbits increased between 1 and 7 days' obstruction and came back toward control levels at 14 days' obstruction. In old rabbits, bladder weight increased after obstruction, reaching a maximum at 3 days and remaining at this level throughout the 14 days. In young rabbits, the expression of ROKalpha increased in 1- to 7-day obstructed groups and decreased in the 14-day group, whereas it increased progressively in the old rabbits at both the mRNA and protein levels. There was a significant decrease in the expression of ROKbeta in young obstructed rabbits, which gradually decreased during the course of 1- to 7-day obstruction period and increased after 14 days of obstruction. In old groups, there was a decrease in expression after 1 day of obstruction and values remained at a decreased level throughout the course of the study. CONCLUSIONS: Young rabbit bladders are better able to adapt to bladder outlet obstruction and ROK isoforms respond in a similar way.

Clinically assessed knee joint laxity as a predictor for reconstruction after an anterior cruciate ligament injury: a prospective study of 100 patients treated with activity modification and rehabilitation.

BACKGROUND: The association of early knee joint laxity with the need for later reconstruction of the anterior cruciate ligament has not been extensively studied. HYPOTHESIS: The grade of knee laxity can be used as an early predictor of the need for later reconstruction. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS: One hundred consecutive patients with an acute arthroscopically verified total anterior cruciate ligament rupture were followed prospectively for 15 years. Lachman and pivot-shift tests were performed with the patient under general anesthesia before arthroscopy. After 3 months, the tests were repeated in an ordinary clinical setting. All patients underwent rehabilitation as the first choice of treatment. Anterior cruciate ligament reconstruction was performed only in cases of significant reinjuries (n = 16) or reparable meniscal lesions (n = 6) at a mean of 4 years after injury (range, 4 months-11 years). After 15 years, 94 patients were available for follow-up. RESULTS: Of the later reconstructed patients (n = 18), 82% had a high-grade Lachman test under anesthesia compared with 63% of the nonreconstructed patients (n = 45; P = .048). At 3 months, 44% of the nonreconstructed patients (n = 32) had a high-grade Lachman test compared with 82% of the reconstructed patients (n = 18; P = .007). Twenty-five patients displayed a normal pivot-shift test at 3 months, of whom 1 underwent later reconstruction (P = .009). A high-grade pivot-shift test at 3 months was associated with an 11.4 relative risk for reconstruction. CONCLUSION: A positive pivot-shift test at 3 months after injury in an awake patient is the strongest predictor for the future need for reconstruction. Furthermore, a normal pivot-shift test at 3 months indicates a low risk for reconstruction and is characteristic for copers.