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OBJECTIVE: The objective of our study was to determine the prevalence of incidental pheochromocytomas, whether their imaging characteristics differ from those of pheochromocytomas in symptomatic patients, and whether they differ from adenomas using CT densitometry. MATERIALS AND METHODS: The records from 335 adrenalectomies performed at our institution from 1995 to 2002 were reviewed, and 71 pheochromocytomas were identified. Thirty-three patients had CT examinations performed at our institution that were available for retrospective review. From electronic and hard-copy medical records, patient age and sex, the indications for imaging, and biochemistry activity were recorded. Pheochromocytomas were classified as symptomatic or incidental on the basis of clinical presentation. These groups were compared for differences in patient age, adrenal mass volume and maximal diameter based on CT dimensions, attenuation on unenhanced CT, attenuation on enhanced CT during the portal phase, the presence of calcifications, low attenuation or cystic changes, biochemical activity, and hypertension. Statistical significance was assessed with the Student's t test or chi-square test, as appropriate. RESULTS: Nineteen incidental (57.6%) and 14 symptomatic (42.4%) adrenal pheochromocytomas were in the study. There was a significant difference between the two groups as to whether hypertension was present (incidental, 10/19 [52.6%]; symptomatic, 14/14 [100%]; p = 0.0025). We found a trend toward calcification present in more symptomatic patients (incidental, 0/19 [0%]; symptomatic, 4/14 [28.6%]; p = 0.0670). No statistically significant difference was noted in the mean patient age (incidental, 51.7 years; symptomatic, 45.9 years), mean volume of the mass (incidental, 74.0 cm(3); symptomatic, 78.2 cm(3)), mean maximal diameter of the mass (incidental, 5.26 cm; symptomatic, 5.33 cm), mean attenuation on unenhanced CT (incidental, 36.6 H; symptomatic, 34.2 H), mean attenuation on enhanced CT (incidental, 93.7 H; symptomatic, 104.3 H), necrosis score or biochemical activity (incidental, 17/18 [94.4%]; symptomatic, 12/14 [85.7%]). No attenuation value of any pheochromocytoma was less than 10 H on unenhanced CT (median, 35 H; range, 17-59 H). CONCLUSION: In our study population, 57.6% of the pheochromocytomas were incidental, more than in most reported series. A history of hypertension was more frequent in the symptomatic group (p = 0.0025), but no radiologic parameters that allow differentiation of incidental and symptomatic pheochromocytomas were found. None of the pheochromocytomas had attenuation values of less than 10 H on unenhanced CT scans.
Human narcolepsy is a chronic sleep disorder affecting 1:2000 individuals. The disease is characterized by excessive daytime sleepiness, cataplexy and other abnormal manifestations of REM sleep, such as sleep paralysis and hypnagogic hallucinations. Recently, it was discovered that the pathophysiology of (idiopathic) narcolepsy-cataplexy is linked to hypocretin ligand deficiency in the brain and cerebrospinal fluid (CSF), as well as the positivity of the human leukocyte antigen (HLA) DR2/DQ6 (DQB1*0602). The symptoms of narcolepsy can also occur during the course of other neurological conditions (i.e. symptomatic narcolepsy). We define symptomatic narcolepsy as those cases that meet the International Sleep Disorders Narcolepsy Criteria, and which are also associated with a significant underlying neurological disorder that accounts for excessive daytime sleepiness (EDS) and temporal associations. To date, we have counted 116 symptomatic cases of narcolepsy reported in literature. As, several authors previously reported, inherited disorders (n=38), tumors (n=33), and head trauma (n=19) are the three most frequent causes for symptomatic narcolepsy. Of the 116 cases, 10 are associated with multiple sclerosis, one case of acute disseminated encephalomyelitis, and relatively rare cases were reported with vascular disorders (n=6), encephalitis (n=4) and degeneration (n=1), and hererodegenerative disorder (three cases in a family). EDS without cataplexy or any REM sleep abnormalities is also often associated with these neurological conditions, and defined as symptomatic cases of EDS. Although it is difficult to rule out the comorbidity of idiopathic narcolepsy in some cases, review of the literature reveals numerous unquestionable cases of symptomatic narcolepsy. These include cases with HLA negative and/or late onset, and cases in which the occurrences of the narcoleptic symptoms are parallel with the rise and fall of the causative disease. A review of these cases (especially those with brain tumors), illustrates a clear picture that the hypothalamus is most often involved. Several cases of symptomatic cataplexy (without EDS) were also reported and in contrast, these cases appear to be often associated with non-hypothalamic structures. CSF hypocretin-1 measurement were also carried out in a limited number of symptomatic cases of narcolepsy/EDS, including narcolepsy/EDS associated with tumors (n=5), head trauma (n=3), vascular disorders (n=5), encephalopathies (n=3), degeneration (n=30), demyelinating disorder (n=7), genetic/congenital disorders (n=11) and others (n=2). Reduced CSF hypocretin-1 levels were seen in most symptomatic narcolepsy cases of EDS with various etiologies and EDS in these cases is sometimes reversible with an improvement of the causative neurological disorder and an improvement of the hypocretin status. It is also noted that some symptomatic EDS cases (with Parkinson diseases and the thalamic infarction) appeared, but they are not linked with hypocretin ligand deficiency. In contrast to idiopathic narcolepsy cases, an occurrence of cataplexy is not tightly associated with hypocretin ligand deficiency in symptomatic cases. Since CSF hypocretin measures are still experimental, cases with sleep abnormalities/cataplexy are habitually selected for CSF hypocretin measures. Therefore, it is still not known whether all or a large majority of cases with low CSF hypocretin-1 levels with CNS interventions, exhibit EDS/cataplexy. It appears that further studies of the involvement of the hypocretin system in symptomatic narcolepsy and EDS are helpful to understand the pathophysiological mechanisms for the occurrence of EDS and cataplexy.
OBJECTIVE: To evaluate the reliability of transcranial Doppler ultrasound in detecting symptomatic vasospasm in patients after aneurysmal subarachnoid hemorrhage and monitoring response after hypertensive and endovascular treatments. DESIGN: Retrospective chart review. SETTING: Neurosciences critical care unit in a tertiary-care university hospital. PATIENTS: All patients admitted to a neurosciences critical care unit with the diagnosis of subarachnoid hemorrhage between January 1990 and June 1997. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: We reviewed transcranial Doppler ultrasound data of 199 patients; 55 had symptomatic vasospasm. Clinical symptoms and corresponding vascular distributions were identified, as was angiographic vasospasm (n = 35). The sensitivity and specificity of transcranial Doppler ultrasound for anterior circulation vessels were calculated by using a mean cerebral blood flow velocity criterion of >120 cm/sec. Clinical diagnosis of symptomatic vasospasm was used as the standard to determine sensitivity and specificity of transcranial Doppler ultrasound and cerebral angiography. The sensitivity of transcranial Doppler ultrasound for anterior circulation in patients with symptomatic vasospasm was 73% with a specificity of 80%. The sensitivity of cerebral angiography was 80%. For individual vessels, the sensitivity and specificity of transcranial Doppler ultrasound were middle cerebral artery, 64% and 78%; anterior cerebral artery, 45% and 84%; and internal carotid artery, 80% and 77%, respectively. The mean times for symptomatic and transcranial Doppler ultrasound signs of vasospasm presentation were 6.4 +/- 2 and 6.1 +/- 3 days, respectively. In patients without symptomatic vasospasm, the mean time for mean cerebral blood flow velocities >120 cm/sec was 7.0 +/- 3 days (p <.05). Symptomatic vasospasm also was associated with thickness of clot on head computed tomography scan and rapidly increasing mean cerebral blood flow velocities. Transcranial Doppler ultrasound signs of vasospasm improved after endovascular treatment in 30 patients. CONCLUSIONS: The reliability of transcranial Doppler ultrasound was better at detecting high mean cerebral blood flow velocities in patients with symptomatic vasospasm related to middle cerebral and internal carotid artery distributions than for anterior cerebral artery distribution. Transcranial Doppler ultrasound was as sensitive as cerebral angiography at detecting symptomatic vasospasm. High mean cerebral blood flow velocities can be apparent before the presence of symptomatic vasospasm. Daily transcranial Doppler ultrasound monitoring could provide early identification of patients with aneurysmal subarachnoid hemorrhage who are at high risk for symptomatic vasospasm and may be helpful at following success of endovascular treatment.
STUDY DESIGN: This was a prospective observational study of patients with low back pain and those without after laminotomy and discectomy. OBJECTIVES: To determine, using a strict experimental design, the relative pain intensity response to provocative discography in symptomatic and asymptomatic subjects after lumbar discectomy for intervertebral disc herniation. BACKGROUND: Provocative discography frequently is used to evaluate persistent or recurrent low back pain syndromes in patients who have undergone posterior discectomy. The validity of interpreting painful injections during this procedure has not been critically assessed. The prevalence of significantly painful disc injections in a group with good outcomes after surgery is not known. Knowing the rates of significantly painful injections in asymptomatic patients after lumbar discectomy may clarify the meaning of painful injections in symptomatic patients. METHODS: From a cohort of 240 patients who had undergone single-level limited discectomy for sciatica, 20 asymptomatic volunteers were recruited for experimental three-level lumbar discography. Inclusion criteria required nearly perfect scores on standardized back pain rating instruments, no other spinal pathology, and normal psychometric screening. A control group of 27 symptomatic patients, after single-level discectomy with intractable low back pain syndrome, and without other spinal pathology, underwent discography. Seven patients in the control group had normal psychometric tests. Experienced raters who were blinded to control versus experimental status of the subjects scored the magnetic resonance imaging, discogram, psychometric tests, and discography videotapes of the subjects' pain behavior. RESULTS: There were 8 of 20 (40%) positive injections of discs that had previous surgery in the asymptomatic group and 17 of 27 (63%) positive injections in the symptomatic group. Specifically with regard to the symptomatic group, there were 3 of 7 (43%) positive injections (all concordant) in patients with normal psychometric scores, as compared with 14 of 20 (70%) positive injections (12 concordant) in patients with abnormal psychometric scores. Injections of discs that had previous surgery resulted in a mean pain score of 2.1 of 5 in the asymptomatic group, 2.1 in the symptomatic group with normal psychometric scores, and 3.4 in the symptomatic group with abnormal psychometric scores. Of the discs not treated with surgery, 2 were positive in the asymptomatic group (10%), 3 in 2 symptomatic subjects with normal psychological testing (29), and 18 in 13 symptomatic subjects with abnormal psychometric testing (76%). CONCLUSIONS: A high percentage of asymptomatic patients with normal psychometric testing who previously have undergone lumbar discectomy will have significant pain on injection of their discs that had previous surgery (40%). This is not significantly different from the experience of symptomatic patients with normal psychometric testing undergoing discography on discs that had previous surgery. Patients with abnormal psychological profiles have significantly higher rates of positive disc injections than either asymptomatic volunteers or symptomatic subjects with normal psychological screening.
Percutaneous vertebroplasty (PVP) is an efficient procedure to treat pain due to osteoporotic vertebral compression fractures (OVCFs). However, some patient populations experience recurrent vertebral fracture after initial successful procedure. There are a lot of literatures about the effectiveness of this procedure but few concerning the development of recurrent, new compression fracture. This is a retrospective review of all PVPs performed in author's institution from September 1999 to December 2001 to investigate the factors related to the development of new symptomatic OVCFs after PVPs. A retrospective review of 244 cases of PVP for symptomatic OVCFs at 382 levels was performed. Sociodemographic, clinical, radiologic, and procedural data were analyzed and compared between the two patient groups (control group : no further symptomatic OVCFs after the initial PVP, "new symptomatic fracture" group: with newly developed symptomatic OVCF). Statistical analysis was performed between the variables of the two groups. Survival analysis was performed using the Kaplan-Meier method. Over all, 38 among 244 treated patients (15.6%) had experienced newly developed symptomatic OVCF(s) during the follow up period (mean 52.5 months). Old age and the presence of multiple treated vertebrae at the initial PVP were assessed as a strong parameter for predicting new symptomatic OVCF. With increasing preoperative wedging deformity the risk of developing new symptomatic OVCF decreased. The Kaplan-Meier estimate of the 1 year fracture-free rate was 92.2%. The Kaplan-Meier curve showed that 7.8% of the patients would experience new symptomatic OVCF within 1 year after initial PVP. A preoperative only mild wedge deformity of the fractured vertebra(e) could indicate the increased risk of developing new symptomatic OVCF after vertebroplasty.
OBJECTIVE: While symmetry and clustering of radiographic hand osteoarthritis (OA) have been described in middle-aged women, these have not been studied in elderly individuals and similar investigations are lacking for symptomatic hand OA. The goal of this study was to study patterns of joint involvement in symptomatic hand OA among elderly Caucasian men and women. METHODS: Using data from the Framingham Osteoarthritis Study, we defined a joint as having symptomatic OA if it had symptoms and radiographic OA (Kellgren and Lawrence grade > or =2). We assessed clustering of symptomatic OA using a chi(2)-test and evaluated the interrelationship of occurrence of symptomatic OA among different joints with generalized estimating equations. RESULTS: Of 976 subjects (age 71-99 yr, 36% men) examined, symptomatic OA more often affected multiple hand joints in an individual than would be expected by chance (P<0.001). The presence of symptomatic OA at a particular joint was strongly associated with symptomatic OA in the same joint of the opposite hand, followed by other joints in the same row of the same hand, and then other joints in the same ray of the same hand. The symmetrical pattern of symptomatic OA was more apparent in women than in men. CONCLUSION: Our study demonstrates that symptomatic OA often affects multiple hand joints, and is more likely to cluster by row than by ray. The disease also occurs in a remarkably symmetrical pattern, especially in women.
PURPOSE: To prospectively evaluate magnetic resonance (MR) imaging findings of abductor tendons and muscles in asymptomatic and symptomatic patients after lateral transgluteal total hip arthroplasty (THA). MATERIALS AND METHODS: The institutional review board approved the study, and all patients provided informed consent. Two musculoskeletal radiologists blinded to clinical information analyzed triplanar MR images of the greater trochanter obtained in 25 patients without and 39 patients with trochanteric pain and abductor weakness after THA. Tendon defects, diameter, signal intensity, and ossification; fatty atrophy; and bursal fluid collections were assessed. In 14 symptomatic patients, MR imaging and surgical findings were correlated. Differences in the frequencies of findings between the two groups were tested for significance by using chi2 analysis. RESULTS: Tendon defects were uncommon in asymptomatic patients and significantly more frequent in symptomatic patients: Two asymptomatic versus 22 symptomatic patients had gluteus minimus defects (P < .001); four asymptomatic versus 24 symptomatic patients, lateral gluteus medius defects (P < .001); and no asymptomatic versus seven symptomatic patients, posterior gluteus medius defects (P = .025). In both patient groups, tendon signal intensity changes were frequent, with the exception of those in the posterior gluteus medius tendon, which demonstrated these changes more frequently in symptomatic patients (in 23 vs five asymptomatic patients, P = .002). Tendon diameter changes were frequent in both groups but significantly (P = .001 to P = .009) more frequent in symptomatic patients (all tendon parts). Fatty atrophy was evident in the anterior two-thirds of the gluteus minimus muscle in both groups, without significant differences. In the posterosuperior third of the gluteus minimus muscle, however, differences in fatty atrophy between the two groups were significant (P = .026). Fatty atrophy of the gluteus medius muscle was present in symptomatic patients only, with significant differences among all muscle parts. Bursal fluid collections were more frequent in symptomatic patients (n = 24) than in asymptomatic patients (n = 8, P = .021). The MR imaging-based diagnosis was confirmed in all 14 patients who underwent revision surgery. CONCLUSION: Abductor tendon defects and fatty atrophy of the gluteus medius muscle and the posterior part of the gluteus minimus muscle are uncommon in asymptomatic patients after THA.
OBJECTIVE: The purpose of this study was to evaluate the prevalence of MR abnormalities of the knee on the symptomatic and contralateral asymptomatic sides in patients with suspected meniscal tears. SUBJECTS AND METHODS. One hundred patients (mean age, 42.7 years; range, 18-73 years) referred for suspected meniscal tears were prospectively examined with MRI of both knees when the contralateral knee was asymptomatic. The prevalence of various types of meniscal tears and other MR abnormalities was determined. RESULTS: Meniscal tears were found in 57 symptomatic knees and in 36 contralateral asymptomatic knees. In those 57 patients with a meniscal tear on the symptomatic side, the prevalence of asymptomatic tears in the contralateral side was 63% (36/57). Horizontal or oblique meniscal tears were found medially in 32 and laterally in 11 symptomatic knees, and medially in 29 and laterally in eight asymptomatic knees. Radial, vertical, complex, or displaced tears were found medially in 18 and laterally in five symptomatic knees, and medially in five and laterally in none of the asymptomatic knees. Collateral ligament abnormalities were found in 53 symptomatic knees and in six asymptomatic knees. Pericapsular soft-tissue abnormalities were found in 64 symptomatic and in 12 asymptomatic knees. Edema-like bone marrow abnormalities were found in 36 symptomatic and in three asymptomatic knees. CONCLUSION: Horizontal or oblique meniscal tears are frequently encountered in both asymptomatic and symptomatic knees and may not always be related to symptoms. However, radial, vertical, complex, or displaced meniscal tears and abnormalities of the collateral ligaments, pericapsular soft tissues, and bone marrow are found almost exclusively on the symptomatic side and appear to be clinically more meaningful.
OBJECTIVE: We previously reported an increased preponderance of a broad range of autoantibodies in symptomatic women with silicone breast implants. The objective of this study was to investigate the frequency of autoantibody production in asymptomatic compared to symptomatic women with silicone implants. One hundred twenty-two asymptomatic women were recruited to our center for autoantibody detection through an advocate dealing with breast implant liabilities. METHODS: Autoantibody detection in 86 asymptomatic women was done blindly on a panel of 15 different antibodies (dsDNA, ssDNA, histones, SSA/Ro, SSB/La, RNP, cardiolipin, phosphatidylserine, pyruvate dehydrogenase, Scl-70, NC-1, silicone, collagen I, II, and IV). Clinical variables, specific questioning about related silicone implant symptoms, and a rheumatological examination were performed blindly by a certified rheumatologist. The findings were recorded and at a later stage compared with positive autoantibody detection. The normal control group consisted of age and sex matched Israeli women without known autoimmune disease. In the positive control group were symptomatic women previously tested for antibody production. The autoantibodies were assessed by ELISA. Values from individual patients were considered positive only when greater than 3 standard deviations above the control mean. RESULTS: The mean ages of 86 asymptomatic and 116 symptomatic women were 46.2+/-11.2 and 45.7+/-8.3 years, respectively. Breast implants were in place for a mean period of 8.2+/-5.0 years in the asymptomatic group and 15.0+/-5.6 years in the symptomatic group. The incidence of increased titers of autoantibodies ranged from 2 to 13% for 13 different autoantibodies among asymptomatic women. Among symptomatic women, 20% harbored 4 autoantibodies and 8% had 6 autoantibodies. The most common antibodies in the asymptomatic group were: dsDNA 8%; ssDNA 9%; SSB/La 13%; silicone 9%; collagen II 9%. No autoantibodies were found for NC-1, Scl-70, or RNP. Among the symptomatic group, the most common autoantibodies were histone ribosomal phosphate, SSA, SSB, Scl-70, cardiolipin, phosphatidylserine, GM2-ganglioside, and NC-1. Comparison of autoantibody incidence in asymptomatic and symptomatic women with silicone breast implants revealed an increased incidence of anti-SSB/La and anticollagen II in both groups. Polyclonality was more prominent in the group of symptomatic women with silicone breast implants, but also evident in 3 asymptomatic women. CONCLUSION: The mean duration of implant in the asymptomatic group was significantly less compared with the symptomatic group (p<0.01). The development of autoantibodies may be related to implant duration.
BACKGROUND: Numerous trials and meta-analyses have shown that extended out-of-hospital prophylaxis with low-molecular-weight heparin reduces asymptomatic and symptomatic venous thromboembolism after total hip arthroplasty. We hypothesized that knowledge of the results of screening tests may have resulted in overdiagnosis of symptomatic venous thromboembolism in many of these studies. The purpose of this analysis was to obtain an accurate estimate of the absolute risk reduction (ARR) of symptomatic venous thromboembolism after discharge from hospital in controlled studies that avoided this potential bias for overdiagnosis. METHODS: Articles were identified using MEDLINE, EMBASE, and the Cochrane Library databases (January 1980-April 2002). Studies were eligible if the assessment of symptomatic venous thromboembolism was standardized and performed independently of mandatory objective testing. RESULTS: Two studies (907 patients) were eligible for assessment of symptomatic venous thromboembolism, 5 studies (1917 patients) for symptomatic pulmonary embolism, and 7 studies (2425 patients) for fatal pulmonary embolism. In controls vs extended treatment groups, after hospital discharge, the frequency of symptomatic venous thromboembolism was 2.7% vs 1.1% (ARR, 1.56%; 95% confidence interval [CI], -0.21% to 3.3%; number needed to treat, 64); symptomatic pulmonary embolism was 0.36% vs 0% (ARR, 0.36%; 95% CI, -0.3% to 1.36%; number needed to treat, 278); and fatal pulmonary embolism was 0.09% vs 0% (ARR, 0.09%; 95% CI, -0.08% to 0.27%; number needed to treat, 1093). CONCLUSIONS: The absolute reduction in symptomatic venous thromboembolism attributed to extended prophylaxis in some studies and meta-analyses seems to have been overestimated.
OBJECTIVE: To differentiate MR imaging characteristics of symptomatic as compared with asymptomatic Achilles tendons. DESIGN: 1.5 T MR images of 94 feet (88 patients) with "abnormal" MR examinations were retrospectively evaluated and clinically correlated. Two masked, independent observers systematically evaluated for intratendon T2 signal, tendon thickness, presence of peritendonitis, retrocalcaneal bursal fluid volume, pre-Achilles edema, bone marrow edema at the Achilles insertion, and tears (interstitial, partial, complete). These findings were correlated with symptoms (onset and duration) and physical examination results (tenderness, palpable defects, increased angle of resting dorsiflexion). RESULTS: Of the 94 ankles, 64 ankles (32 females, 29 males) were clinically symptomatic. No relationship between Achilles tendon disorders and age or gender was identified. Asymptomatic Achilles tendons frequently demonstrated mild increased intratendon signal (21/30), 0.747 cm average tendon thickness, peritendonitis (11/30), pre-Achilles edema (12/30), and 0.104 ml average retrocalcaneal bursal fluid volume. Symptomatic patients had thicker tendons (0.877 cm), greater retrocalcaneal fluid volume (0.278 ml), more frequent tears (23/64), a similar frequency of peritendonitis (22/64) but less frequent pre-Achilles edema (18/64). Sixty-four percent of the Achilles tendon tears were interstitial. Except for two interstitial tears in control patients, the majority of Achilles tears were in symptomatic patients (14/16). Only symptomatic tendons demonstrated partial or complete tendon tears. In addition, calcaneal edema was found almost exclusively in actively symptomatic patients. Thicker tendons were associated more often with chronic symptoms and with tears. When present in symptomatic patients, peritendonitis was usually associated with acute symptoms. The presence of pre-Achilles edema, however, did not distinguish acute from chronic disorders. CONCLUSION: There is significant overlap of MR findings in symptomatic and asymptomatic Achilles tendons. Furthermore, there is apparently a spectrum of disease in symptomatic tendons ranging from subtle intratendinous and peritendinous signal to partial and complete tendon tear.
Patients with rotator cuff tears have varying degrees of symptom expression. Our purpose was to evaluate the differential firing patterns of the rotator cuff, deltoid, and scapular stabilizer muscle groups in normal control subjects and in patients with symptomatic and asymptomatic 2-tendon rotator cuff tears. Eighteen subjects were evaluated: six normal subjects and twelve with 2-tendon cuff tears (six asymptomatic and six symptomatic). All cuff tear patients had magnetic resonance imaging (MRI) scans documenting superoposterior tear configurations involving the supraspinatus and infraspinatus tendons; all normal subjects had an ultrasound examination confirming the absence of cuff pathology. Subjects were grouped based on shoulder examination and outcomes questionnaires. Asymptomatic patients had minimal pain (<3 on the visual analog scale and no loss of active range of motion compared with the contralateral side); symptomatic patients had pain greater than 3 on the visual analog scale and decreased range of motion compared with the contralateral side (>10 degrees of motion loss). Electromyographic activity from 12 muscles and kinematic data were collected simultaneously during 10 functional tasks. Both symptomatic and asymptomatic cuff subjects demonstrated a trend toward increased muscle activation during all tasks compared with normal subjects. During the internal rotation tasks, asymptomatic patients had significantly greater (P<.05) subscapularis activity than symptomatic patients (65% maximal voluntary contraction [MVC] vs 42% MVC). During the carrying task, asymptomatic patients demonstrated significantly less (P<.03) upper trapezius muscle activation than symptomatic patients (16% MVC vs 50% MVC). During shoulder elevation tasks, symptomatic patients had significantly greater supraspinatus (52% MVC vs 28% MVC, P<.03), infraspinatus (32% MVC vs 16% MVC, P<.05), and upper trapezius (39% MVC vs 20% MVC, P<.04) muscle activation compared with asymptomatic patients. During heavy elevation (8 lb), asymptomatic patients showed a trend toward increased activation (P<.06) of the subscapularis compared with symptomatic patients (34% MVC vs 21% MVC). Differential shoulder muscle firing patterns in patients with rotator cuff pathology may play a role in the presence or absence of symptoms. Asymptomatic subjects demonstrated increased firing of the intact subscapularis, whereas symptomatic subjects continued to rely on torn rotator cuff tendons and periscapular muscle substitution, resulting in compromised function.
PURPOSE: The structural features that underlie carotid plaque disruption and symptoms are largely unknown. We have previously shown that the chemical composition and structural complexity of critical carotid stenoses are related to plaque size regardless of symptoms. To further determine whether the spatial distribution of individual plaque components in relation to the lumen corresponds to symptomatic outcome, we evaluated 99 carotid endarterectomy plaques. METHODS: Indications for operation were symptomatic disease in 59 instances (including hemispheric transient ischemic attack in 29, stroke in 19, and amaurosis fugax in 11) and angiographic asymptomatic stenosis > 75% in 40. Plaques removed after remote symptoms beyond 6 months were excluded. Histologic sections from the most stenotic region of the plaque were examined using computer-assisted morphometric analysis. The percent area of plaque cross-section occupied by necrotic lipid core with or without associated plaque hematoma, by calcification, as well as the distance from the lumen or fibrous cap of each of these features, were determined. The presence of foam cells, macrophages, and inflammatory cell collections within, on, or just beneath the fibrous cap was taken as an additional indication of plaque neoformation. RESULTS: The mean percent angiographic stenosis was 82% +/- 11% and 79% +/- 13% for the asymptomatic and symptomatic groups, respectively (p > 0.05). The necrotic core was twice as close to the lumen in symptomatic plaques when compared with asymptomatic plaques (0.27 +/- 0.3 mm vs 0.5 +/- 0.5 mm; p < 0.01). The percent area of necrotic core or calcification was similar for both groups (22% vs 26% and 7% vs 6%, respectively). There was no significant relationship to symptom production of either the distance of calcification from the lumen or of the percent area occupied by the lipid necrotic core or calcification. The number of macrophages infiltrating the region of the fibrous cap was three times greater in the symptomatic plaques compared with the asymptomatic plaques (1114 +/- 1104 vs 385 +/- 622, respectively, p < 0.009). Regions of fibrous cap disruption or ulceration were more commonly observed in the symptomatic plaques than in the asymptomatic plaques (32% vs 20%). None of the demographic or clinical atherosclerosis risk factors distinguished between symptomatic and asymptomatic plaques. CONCLUSIONS: These findings indicate that proximity of plaque necrotic core to the lumen and cellular indicators of plaque neoformation or inflammatory reaction about the fibrous cap are associated with clinical ischemic events. The morphologic complexity of carotid stenoses does not appear to determine symptomatic outcome but rather the topography of individual plaque components in relation to the fibrous cap and the lumen. Imaging techniques that precisely resolve the position of the necrotic core and evidence of inflammatory reactions within carotid plaques should help identify high-risk stenoses before disruption and symptomatic carotid disease.
OBJECTIVES: To evaluate the effect of alendronate on the occurrence rate of multiple svmptomatic fractures and on the risk of multiple symptomatic fractures (likelihood of having more than one fracture diagnosed because of the symptoms the fractures caused over the study period) among women with osteoporosis. DESIGN: Primary analysis of data from a randomized, placebo-controlled, double-blind trial. SETTING: Eleven community-based clinical research centers. PARTICIPANTS: Subset of women enrolled in the Fracture Intervention Trial: aged 55 to 81 and having at least one morphometric vertebral fracture at baseline (n=2,027) or having no vertebral fracture but meeting prevailing World Health Organization bone mineral density criteria for osteoporosis (T-score < or =2.5 at the femoral neck)(n = 1,631). INTERVENTION: All participants reporting calcium intake of 1,000 mg/day or less received a supplement of 500 mg calcium and 250 IU cholecalciferol. Participants were randomly assigned to placebo or alendronate sodium (5 mg/day for 2 years and 10 mg/day for the remainder of the study). Average total follow-up was 4.3 years. MEASUREMENTS: Symptomatic fractures were diagnosed by personal physicians and confirmed by review of radiological data by an expert committee blinded to treatment assignments. RESULTS: Eighty-six of 1,817 women receiving placebo experienced multiple symptomatic fractures during the follow-up period, compared with 51 of 1,841 receiving alendronate. Reduction of risk for multiple symptomatic fractures combined was 42% (relative risk (RR) = 0.58, 95% confidence interval (CI) = 0.41, 0.81) and for multiple symptomatic vertebral fractures was 84% (RR = 0.16,95% Cl = 0.05, 0.42). Cumulative incidence curves showed divergence after as little as 3 months of treatment, with a statistically significant (P = .044) reduction at 6 months for multiple symptomatic vertebral fractures. When all fractures over the follow-up period were included, the occurrence rates of all symptomatic fractures and symptomatic vertebral fractures were 34% and 63% lower, respectively, with alendronate than with placebo. These reductions were sustained during the follow-up period. All reductions in risk were consistent across predefined subgroups: age (<75 vs > or =75), morphometric vertebral fracture(present vs absent), prior clinical fracture since age 45 (yes vs no), and whether the subject had fallen in the 12 months before randomization. CONCLUSIONS: These data demonstrate that treatment with alendronate reduces the risk of multiple symptomatic fractures during a treatment period averaging 4.3 years. The reductions were consistent across prespecified sub-groups. This effect is evident early in treatment and is sustained.
OBJECTIVE: The risk of stroke in patients with recently symptomatic carotid stenosis is considerably higher than in patients with asymptomatic stenosis. In the present study it was hypothesised that excessive platelet activation might partly contribute to this difference. METHODS: A full blood count was done and whole blood flow cytometry used to measure platelet surface expression of CD62P, CD63, and PAC1 binding and the percentage of leucocyte-platelet complexes in patients with acute (0-21 days, n = 19) and convalescent (79-365 days) symptomatic (n = 16) and asymptomatic (n = 16) severe (> or =70%) carotid stenosis. Most patients were treated with aspirin (37.5-300 mg daily) although alternative antithrombotic regimens were more commonly used in the symptomatic group. RESULTS: The mean platelet count was higher in patients with acute and convalescent symptomatic compared with asymptomatic carotid stenosis. There were no significant differences in the median percentage expression of CD62P and CD63, or PAC1 binding between the acute or convalescent symptomatic and asymptomatic patients. The median percentages of neutrophil-platelet (p = 0.004), monocyte-platelet (p = 0.046), and lymphocyte-platelet complexes (p = 0.02) were higher in acute symptomatic than in asymptomatic patients. In patients on aspirin monotherapy, the percentages of neutrophil-platelet and monocyte-platelet complexes (p = 0.03) were higher in acute symptomatic (n = 11) than asymptomatic patients (n = 14). In the convalescent phase, the median percentages of all leucocyte-platelet complexes in the symptomatic group dropped to levels similar to those found in the asymptomatic group. CONCLUSION: Increased platelet count and leucocyte-platelet complex formation may contribute to the early excess risk of stroke in patients with recently symptomatic carotid stenosis.