Vascular pentraxin 3 controls arterial thrombosis by targeting collagen and fibrinogen induced platelets aggregation.

AIM: The long pentraxin PTX3 plays a non-redundant role during acute myocardial infarction, atherosclerosis and in the orchestration of tissue repair and remodeling during vascular injury, clotting and fibrin deposition. The aim of this work is to investigate the molecular mechanisms underlying the protective role of PTX3 during arterial thrombosis. METHODS AND RESULTS: PTX3 KO mice transplanted with bone marrow from WT or PTX3 KO mice presented a significant reduction in carotid artery blood flow following FeCl3 induced arterial thrombosis (-80.36±11.5% and -95.53±4.46%), while in WT mice transplanted with bone marrow from either WT or PTX3 KO mice, the reduction was less dramatic (-45.55±1.37% and -53.39±9.8%), thus pointing to a protective effect independent of a hematopoietic cell's derived PTX3. By using P-selectin/PTX3 double KO mice, we further excluded a role for P-selectin, a target of PTX3 released by neutrophils, in vascular protection played by PTX3. In agreement with a minor role for hematopoietic cell-derived PTX3, platelet activation (assessed by flow cytometric expression of markers of platelet activation) was similar in PTX3 KO and WT mice as were haemostatic properties. Histological analysis indicated that PTX3 localizes within the thrombus and the vessel wall, and specific experiments with the N-terminal and the C-terminal PTX3 domain showed the ability of PTX3 to selectively dampen either fibrinogen or collagen induced platelet adhesion and aggregation. CONCLUSION: PTX3 interacts with fibrinogen and collagen and, by dampening their pro-thrombotic effects, plays a protective role during arterial thrombosis.

Evaluation of Mother's Stress during Hospitalization Can Influence the Breastfeeding Rate. Experience in Intensive and Non Intensive Departments.

A mother's milk offers several benefits to infant's health, but, some factors may lead to a reduction in the duration of breastfeeding, such as maternal stress. The objective of our study is to determine if the rate of breastfeeding can be influenced by stress induced by infants' hospitalization. A preliminary observational non-randomized study was carried out in Bambino Gesù Children's Hospital between October 2016 and January 2017, in order to elucidate a possible relationship between breastfeeding and maternal stress, linked to hospitalization. We modeled the modified version of the PSS NICU (Parental Stressor Scale-neonatal intensive care unit) questionnaire, which investigated parental stress during hospitalization. This included 33 items with a score from 0 to 5. The overall score, high stress, was established at 85 points or higher. The principal statistically significant correlation was between 'high PSS score' and reduced breastfeeding during hospitalization (p-value: 0.048; OR: 2.865, 95%; CI: 1.008-8.146). This relation was not influenced by other descriptive characteristics of the mother. The PSS questionnaire can be an instrument to evaluate the influence of stress in breastfeeding and to monitor the rate and success of lactation. Our study highlights that the stress from hospitalization could influence the success of breastfeeding, mostly in intensive settings and during long hospitalizations.

Biological analysis of flexor tendon repair-failure stump tissue: A potential recycling of tissue for tendon regeneration.

OBJECTIVES: Re-rupture is common after primary flexor tendon repair. Characterization of the biological changes in the ruptured tendon stumps would be helpful, not only to understand the biological responses to the failed tendon repair, but also to investigate if the tendon stumps could be used as a recycling biomaterial for tendon regeneration in the secondary grafting surgery. METHODS: A canine flexor tendon repair and failure model was used. Following six weeks of repair failure, the tendon stumps were analyzed and characterized as isolated tendon-derived stem cells (TDSCs). RESULTS: Failed-repair stump tissue showed cellular accumulation of crumpled and disoriented collagen fibres. Compared with normal tendon, stump tissue had significantly higher gene expression of collagens I and III, matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF). The stump TDSCs presented both mesenchymal stem and haematopoietic cell markers with significantly increased expression of CD34, CD44, and CD90 markers. Stump TDSCs exhibited similar migration but a lower proliferation rate, as well as similar osteogenic differentiation but a lower chondrogenic/adipogenic differentiation capability, compared with normal TDSCs. Stump TDSCs also showed increasing levels of SRY-box 2 (Sox2), octamer-binding transcription factor 4 (Oct4), tenomodulin (TNMD), and scleraxis (Scx) protein and gene expression. CONCLUSION: We found that a failed repair stump had increased cellularity that preserved both mesenchymal and haematopoietic stem cell characteristics, with higher collagen synthesis, MMP, and growth factor gene expression. This study provides evidence that tendon stump tissue has regenerative potential.Cite this article: C-C. Lu, T. Zhang, R. L. Reisdorf, P. C. Amadio, K-N. An, S. L. Moran, A. Gingery, C. Zhao. Biological analysis of flexor tendon repair-failure stump tissue: A potential recycling of tissue for tendon regeneration. Bone Joint Res 2019;8:232-245. DOI: 10.1302/2046-3758.86.BJR-2018-0239.R1.

The biomechanics of subsynovial connective tissue in health and its role in carpal tunnel syndrome.

Carpal Tunnel Syndrome (CTS) is the most common surgically treated problem in the hand. Aside from the neuropathy itself, the most common findings are fibrosis of the subsynovial connective tissue (SSCT) and increased intra carpal tunnel pressure. Normally, the SSCT is a multilayer tissue interspersed among the carpal tendons and nerve. As the tendons move, successive SSCT layers are recruited, forming a gliding unit and providing a limit to differential movement. Exceeding this limit, damages the SSCT as has been shown in both cadavers and animal models. This damage leads to a non-inflammatory response with progressive fibrosis and nerve ischemia leaving the SSCT more susceptible to injury. Although the direct consequences for patients are not fully understood, ultrasound research shows that this fibrosis restricts median nerve displacement during tendon loading. This article aims to provide insights into the mechanical properties of SSCT described so far and place it in the context of CTS pathophysiology. A theoretical damage model concerning the SSCT is proposed showing a chain of events and vicious cycles that could lead to the nerve compression as it is found in CTS. Although not complete, this model could explain the pathophysiological pathway of idiopathic CTS.

Unequal decrease in bone density of lumbar spine and ultradistal radius in Colles' and vertebral fracture syndromes.

We measured bone mineral density (BMD) at the lumbar spine (LS-BMD) and ultradistal radius (UDR-BMD) in 42 postmenopausal normal women and in 108 postmenopausal osteoporotic women (55 with vertebral fracture, 34 with Colles' fracture, and 19 with both fractures). By receiver operating characteristic analysis, LS-BMD was better than UDR-BMD (P less than 0.01) as an indicator of vertebral fracture; the converse was true for Colles' fracture (P less than 0.01). Although UDR-BMD and LS-BMD were lower in each of the three fracture groups than in controls (P less than 0.01), the pattern of bone loss differed (P less than 0.001, analysis of variance): with vertebral fracture, LS-BMD decreased relatively more than UDR-BMD; with Colles' fracture, UDR-BMD decreased relatively more than LS-BMD; and with both fractures, decreases in LS-BMD and UDR-BMD were similar. We conclude that both types of fracture are caused by excessive bone loss but the difference in bone loss at the two sites is a major factor in determining which will fracture.

Phase II trial of a biweekly regimen of fluorouracil and leucovorin plus irinotecan in patients with previously untreated advanced gastric cancer.

To investigate the therapeutic value and safety of the biweekly regimen of 5-fluorouracil (5-FU) and leucovorin (LV) plus irinotecan (CPT-11) in patients with previously untreated advanced gastric cancer (AGC). A total of 50 patients (M/F 35/15; median age = 65) with AGC, none of whom had received chemotherapy for advanced disease, were accrued in this trial. Fifteen patients (30%) were 70 years old or older. At the time of their accrual, cytotoxic chemotherapy, consisting of LV 100 mg/m(2) (2-hour i.v. infusion) followed by 5-FU 400 mg/m(2) (bolus) and 5-FU 600 mg/m(2) (22-hour continuous infusion) on therapeutic days 1 and 2 plus CPT-11 180 mg/m(2) (1-hour infusion) on day 1, was initiated. Treatment courses were repeated every 2 weeks until evidence of progressive disease, unacceptable toxicity or withdrawal of consent. All patients were assessable for toxicity and 48 of 50 for response evaluation, having completed at least four courses of chemotherapy. Complete response was achieved in 2 patients (4%, intent to treat) and partial response in 16 (32%) (overall response rate, 36%; 95% confidence interval [CI]: 22%-50%). Twenty-four patients (48%) had stable disease and 6 patients (16%) progressed. The median time to progression was 8 months (95% CI: 6-10 months) and median overall survival 14 months (95% CI: 6-22 months). Between the subgroups of patients <70 years old and 70 or older, there were no significant differences in efficacy. One toxic death occurred. Treatment tolerance was generally mild to moderate and easy to treat. The main grade 3/4 toxicities were neutropenia (32%), diarrhea (16%), and anemia (8%). Grade 3-4 neutropenia was the only treatment-related serious adverse event significantly more common in patients older than those aged <70 (53.3% vs 22.8%, respectively; P = 0.03). Our data suggest that the biweekly regimen of LV and 5-FU plus CPT-11 in untreated patients with AGC is active and has an acceptable safety profile. Further evaluation of this regimen seems to be warranted in a phase III trial.

The revitalisation of flexor tendon allografts with bone marrow stromal cells and mechanical stimulation: An ex vivo model revitalising flexor tendon allografts.

OBJECTIVES: The present study describes a novel technique for revitalising allogenic intrasynovial tendons by combining cell-based therapy and mechanical stimulation in an ex vivo canine model. METHODS: Specifically, canine flexor digitorum profundus tendons were used for this study and were divided into the following groups: (1) untreated, unprocessed normal tendon; (2) decellularised tendon; (3) bone marrow stromal cell (BMSC)-seeded tendon; and (4) BMSC-seeded and cyclically stretched tendon. Lateral slits were introduced on the tendon to facilitate cell seeding. Tendons from all four study groups were distracted by a servohydraulic testing machine. Tensile force and displacement data were continuously recorded at a sample rate of 20 Hz until 200 Newton of force was reached. Before testing, the cross-sectional dimensions of each tendon were measured with a digital caliper. Young's modulus was calculated from the slope of the linear region of the stress-strain curve. The BMSCs were labeled for histological and cell viability evaluation on the decellularized tendon scaffold under a confocal microscope. Gene expression levels of selected extracellular matrix tendon growth factor genes were measured. Results were reported as mean ± SD and data was analyzed with one-way ANOVAs followed by Tukey's post hoc multiple-comparison test. RESULTS: We observed no significant difference in cross-sectional area or in Young's modulus among the four study groups. In addition, histological sections showed that the BMSCs were aligned well and viable on the tendon slices after two-week culture in groups three and four. Expression levels of several extracellular matrix tendon growth factors, including collagen type I, collagen type III, and matrix metalloproteinase were significantly higher in group four than in group three (p < 0.05). CONCLUSION: Lateral slits introduced into de-cellularised tendon is a promising method of delivery of BMSCs without compromising cell viability and tendon mechanical properties. In addition, mechanical stimulation of a cell-seeded tendon can promote cell proliferation and enhance expression of collagen types I and III in vitro.Cite this article: J. H. Wu, A. R. Thoreson, A. Gingery, K. N. An, S. L. Moran, P. C. Amadio, C. Zhao. The revitalisation of flexor tendon allografts with bone marrow stromal cells and mechanical stimulation: An ex vivo model revitalising flexor tendon allografts. Bone Joint Res 2017;6:179-185. DOI: 10.1302/2046-3758.63.BJR-2016-0207.R1.

Effect of TGF-beta inducible early gene deficiency on flexor tendon healing.

The role of transforming growth factor beta (TGF-beta) in tendon healing is still not clearly established. TGF-beta affects gene expression primarily through the activation of the Smad signaling pathway. The first step in the Smad pathway is the expression of TGF-beta inducible early gene (TIEG). Recently, a TIEG knockout mouse has been developed. The purpose of this study was to examine the healing potential of flexor tendons in mice lacking the TIEG gene, and to further examine what role the TIEG pathway plays in flexor tendon repair. Twenty-two mice, consisting of 11 normal wild-type mice and 11 TIEG knockout mice, were euthanized at 8 to 12 weeks of age. The second through fifth FDL tendons of both hind feet were transected and repaired in zone 2. The repaired tendons were removed from the mice and placed into tissue culture. Tendons were then examined at days 3, 7, 14, 21, and 42 after surgery. Hematoxylin and eosin (HE) staining and immunohistochemical staining for TGF-beta, collagen type I, and collagen type III were performed. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to examine expression of TGF-beta1, beta2, beta3, and collagen type I and III. At 42 days after surgery, HE staining showed coaptation of lacerated tendon ends in both groups. Both groups showed healing of the lacerated tendon, but the chronologic expression pattern of TGF-beta was different between the knockout and normal tendons. TIEG deficient tendons had delayed expression of TGF-beta when compared with control tendons. The collagen mRNA expression pattern was similar with both groups, but the expression level was different, with TIEG knockout tendons having a lower expression of collagen type I mRNA (p < 0.001). TGF-beta is thought to play a major role in tendon healing. Healing of tendons in the TIEG knockout mouse suggests the possibility of tendon healing in the absence of the Smad pathway. The knockout mouse model described in the present study provides a novel means for further understanding of the tendon healing process through isolated deletion of specific growth factors.

Contraction of collagen gels seeded with tendon cells.

Knowledge of the adaptation of the soft tissue to mechanical factors and biomolecules would be essential to better understand the mechanism of tendon injury and to improve the outcome of tendon repair. The responses to these factors could be different for the distinct types of cells in the tendon: cells from the tendon sheath, fibroblasts from the epitenon surface, or fibroblasts from the internal endotenon. In this study, we examined the mechanical and histological characteristics of the rate of contraction of the collagen gel seeded with epitenon and endotenon fibroblasts. The rate of contraction and the mechanical property of the contracted construct depend on the gel concentration and also the treatment of TGF-beta1.

Hyaluronic acid diminishes the resistance to excursion after flexor tendon repair: an in vitro biomechanical study.

Adhesion between the tendon and tendon sheath after primary flexor tendon repair is seen frequently, and postoperative finger function is occasionally unsatisfactory. A reduction of the friction may facilitate tendon mobilization, which in turn may reduce the risk of the adhesion and restriction of range of motion. We considered the possibility of utilizing the hyaluronic acid (HA) as a lubricant. To evaluate the effect of HA, the gliding resistance between the canine flexor digitorum profundus tendon repaired by a modified Kessler suture technique with running epitendinous suture and the annular pulley located on the proximal phalanx (corresponding to the A2 pulley in humans) was evaluated and compared before and after administration of HA. The HA solution measurement groups were identified as follows; intact tendon as a control; repaired tendon; tendon soaked in 0.1, 1, and 10 mg/ml HA. The resistance increased after repairing, then it decreased after soaking in 10 mg/ml HA solution. The results of this study revealed that HA diminishes the excursion resistance after flexor tendon repair. We believe that some style of administration of the HA might reduce the excursion resistance and prevent adhesion until the synovial surface is fully developed.

The role of calcium channel blockers in the treatment of essential hypertension.

Calcium channel blockers, originally developed for the treatment of angina and supraventricular arrhythmias, have been shown to lower elevated blood pressure effectively in hypertensive patients. Verapamil, nifedipine, and diltiazem represent prototype compounds for unique chemical classes with differing pharmacologic properties. These drugs lower elevated blood pressure with efficacy comparable with other commonly used antihypertensives. Combination therapy with other agents usually results in an additive response. Side effects are usually mild and reversible and usually are an extension of the drug's pharmacologic effects. Moreover, adverse metabolic effects on lipid, glucose, or potassium levels are not common. Because of the excellent antihypertensive effects of calcium channel blockers and their potential importance in a variety of other disease states, these agents should be routinely considered for use as a first-line antihypertensive agent in appropriately selected patients with hypertension of any severity as part of a comprehensive plan to minimize cardiovascular risk.

Providing quantitative feedback when teaching tendon repair: a new tool.

Flexor tendon repair remains one of the more difficult technical tasks facing the hand surgeon. A good repair must be both strong and able to glide smoothly through the tendon sheath. The purpose of this study is to present a model that allows surgeons to improve their technique of flexor tendon repair by receiving feedback on these important biomechanical parameters. The set-up requires testing equipment found in most biomechanical laboratories and should be available in many academic medical centres. Preliminary data suggest that receiving feedback about the strength and smoothness of a flexor tendon repair may be a very useful tool in helping surgeons improve the overall quality of their tendon repair technique.

Colles' fracture and bone density of the ultradistal radius.

To determine whether Colles' fracture, generally considered a manifestation of postmenopausal osteoporosis, is associated with a decrease in bone density at the site of fracture, we measured bone mineral density of the ultradistal radius (UDR-BMD) by single-photon absorptiometry with computer-assisted image processing. In 119 normal women (ages 22-92 years), UDR-BMD decreased by 17% between ages 30 and 75 years. From UDR-BMD measurements in these normal women and in 40 women (ages 53-80 years) with Colles' fracture alone, a population-based analysis was made to estimate fracture risk at different values of UDR-BMD. Colles' fracture was uncommon at UDR-BMD greater than 0.40 g/cm2 (the "fracture threshold"). As bone density decreased below this level, fractures became more frequent (a "gradient of risk").

Peripherally acting analgesics.

The therapeutic effect of aspirin and the other nonsteroidal anti-inflammatory drugs derives from the peripheral inhibition of prostaglandin synthetase. Aspirin produces irreversible inhibition, whereas the inhibition triggered by the other nonsteroidal anti-inflammatory drugs is reversible. Despite proved analgesic efficacy, use of aspirin and the nonsteroidal anti-inflammatory drugs may be accompanied by a wide range of side effects of a potentially serious nature. For relief of pain, there appears to be no clear-cut superiority of one nonsteroidal anti-inflammatory drug over another, and patients who fail to respond to one class of nonsteroidal anti-inflammatory drugs may respond to a representative of another class. As with aspirin, it is difficult to demonstrate the superiority of higher doses of these agents over the lower doses. The side-effect profile of non-narcotic analgesics favors acetaminophen, presumably because its inhibition of prostaglandin synthetase occurs centrally. Acetaminophen does not appear to have the same potential for toxicity that is seen with aspirin and other nonsteroidal anti-inflammatory drugs. At dosages up to 4 g per day, acetaminophen compares favorably in analgesic potency to aspirin and other nonsteroidal anti-inflammatory drugs, and it should be considered the treatment of choice for mild-to-moderate pain. Safe conditions for the analgesic use of nonsteroidal anti-inflammatory drugs in children and pregnancy have not been established. Because it is virtually free of side effects, acetaminophen may be the mild analgesic of choice for the pregnant patient. It has been used safely for years in children. Only a limited number of analgesic studies have been conducted in children. The results of analgesic studies carried out in adults are generally recognized as applicable to pain relief in children.

The Mayo Clinic and carpal tunnel syndrome.

A review of the medical records at the Mayo Clinic revealed the evolution of a common clinical condition--carpal tunnel syndrome. Initially, treatment was limited to those patients with the most severe neuropathies and derangements of wrist anatomy. As confidence with the diagnosis and therapy increased, progressively less severe anatomic deformities and then progressively less severe neurologic impairments were considered for surgical management. Documentation shows that the first surgical division of the flexor retinaculum for treatment of distal median neuropathy was performed in 1924, almost a decade earlier than previously thought.

The many faces of carpal tunnel syndrome.

Carpal tunnel syndrome, a common and well-described clinical disorder, usually has been considered a chronic disorder with a fixed set of symptoms and typically affecting middle-aged women. Because of the many variations in its initial clinical manifestations, however, its diagnosis at times can be difficult. In this review, we describe nonclassic manifestations of carpal tunnel syndrome and discuss the differential diagnosis, the importance of electrodiagnostic studies, and treatment modalities.

Effect of feedback on resource use and morbidity in hip and knee arthroplasty in an integrated group practice setting.

OBJECTIVE: To assess the effect of a structured program of feedback about resource utilization and morbidity on resource consumption and complications in an orthopedic surgical practice. DESIGN: We prospectively analyzed use and outcomes before and after an intervention (departmental data presentation). MATERIAL AND METHODS: Feedback on resource utilization and morbidity for 2,820 patients who underwent a primary total hip or knee arthroplasty for a diagnosis of osteoarthritis between Jan. 1, 1990, and Dec. 31, 1992, was provided to members of the orthopedic department of an academic medical center. Data were adjusted for severity of disease. RESULTS: On reassessment 18 months after the beginning of the feedback program, total charges and length of hospital stay for hip or knee arthroplasty were significantly reduced. Interpractitioner variability was also reduced but not significantly. The feedback process was instrumental in identifying a specific complication--pulmonary embolism after bilateral total knee replacement--which was significantly reduced by addition of warfarin prophylaxis. CONCLUSION: The intervention was successful in reducing resource use (length of hospital stay) and complications (pulmonary embolism). In addition, total charges for hip and knee arthroplasty declined significantly at a time when medical center charges overall were increasing. Efforts to maintain continuous improvement will primarily focus on the development of critical pathways.

Value of autonomic testing in reflex sympathetic dystrophy.

OBJECTIVE: To attempt to characterize reflex sympathetic dystrophy (RSD) and to determine factors that would predict a response to sympathetic block. DESIGN: We undertook a retrospective analysis on 396 patients with chronic limb pain referred for autonomic testing during a 5-year period. MATERIAL AND METHODS: Clinical endpoints were relief of pain after sympathetic block and a composite RSD diagnostic probability score, based on the clinical attributes of allodynia, protopathia, swelling, and vasomotor alterations. We compared the results of three autonomic tests--resting sweat output (RSO), resting skin temperature (RST), and quantitative sudomotor axon reflex test (QSART). RESULTS: Increased RSO predicted the diagnosis of RSD with 94% specificity, and the specificity was 98% when RSO was considered in conjunction with an abnormal QSART result, the best laboratory correlate (P = 0.003) of the clinical diagnosis. Shorter duration of pain correlated with a warmer limb (P < 0.001), even in the absence of RSD. Response to a single sympathetic block did correlate with the diagnosis (P = 0.031) but correlated most significantly with short duration of pain in the arm (P = 0.001) and laboratory findings in the leg, where increased RST (P < 0.001) and QSART (P < 0.001) were near-perfect predictors of response. CONCLUSION: Sweating abnormalities correlate strongly with the clinical syndrome of RSD, and alterations in RST may be superior to clinical findings in predicting the response to sympathetic block. The findings provide physiologic support for the unproven view of a natural disease progression ("stages"), with better treatment response and a warmer extremity initially. Because certain physiologic trends occur in all patients, general alterations of autonomic function with pain are suggested.

Comparison of two rapid latex agglutination methods for detection of group A streptococcal pharyngitis.

Throat swabs from 404 patients with suspected pharyngitis were collected using duplicate swabs. Both swabs were used to inoculate 5% sheep blood agar plates, which were incubated in an anaerobic atmosphere for the isolation of Group A streptococci. The throat swabs were tested for the presence of Group A antigen using the Culturette Brand 10-Minute Group A Strep ID kit (Marion Scientific, Kansas City, MO), and the Direct Antigen Identification D.A.I. Strep A Test (Difco Laboratories, Inc., Detroit, MI). We found that 77 of the 404 specimens were culture positive for Group A streptococci. The Strep ID kit had a sensitivity of 83.7% and a specificity of 91.6%. The positive and negative predictive values were 72% and 95.6%, respectively. The D.A.I. test had a sensitivity of 80.2% and a specificity of 100%. The positive and negative predictive values were 100% and 94.5%, respectively. There was not a significant difference in the sensitivity of the two kits (P less than 0.1), but there was a significant difference in the specificity (P less than 0.01).

The effect of tolmetin on the chronic pain and decreased functional capacity associated with degenerative joint disease.

Degenerative joint disease (DJD) is a common disorder characterized by chronic pain and limitation of activity, for which treatment with a nonsteroidal anti-inflammatory drug (NSAID) is often useful. The anti-inflammatory activity of the NSAID tolmetin sodium has been well described, being comparable in efficacy to indomethacin and effective for the relief of the acute and chronic symptoms that accompany DJD. To examine specifically the effect of tolmetin in controlling the pain and functional limitation in DJD of the spine, tolmetin was tested against placebo in a double-blind, two-segment, crossover study. Twenty-six patients (mean age, 62.5 years; range, 42-79 years) received three weeks of tolmetin 1,200 mg/d and three weeks of placebo. The results showed that tolmetin provided significantly greater relief of symptoms than placebo in virtually all measurements of joint pain and stiffness: tenderness, pain at rest, pain on motion, intensity of joint pain (P less than 0.001), and duration of morning stiffness (P = 0.002). Statistically significant improvement was noted in two of the three measures of cervical range of motion (P less than or equal to 0.01) and in all assessments of daily living activities (P = 0.001 in four parameters; P = 0.02 in a fifth parameter). Global evaluations of response to treatment by both patients and investigator also demonstrated significant effects (P less than or equal to 0.002). Significantly more placebo patients (13 of 26) than tolmetin patients (two of 26) found the medication ineffective and discontinued treatment prematurely (P = 0.01). No serious or limiting adverse reactions were seen during placebo or tolmetin therapy. The most frequently reported side effects on both therapies were gastrointestinal.(ABSTRACT TRUNCATED AT 250 WORDS)