Buffalo General Medical Center

The accepted standard treatment of relapsing multiple sclerosis consists of medications for disease symptoms, including treatment for acute exacerbations. However, currently there is no therapy that alters the progression of physical disability associated with this disease. The purpose of this study was to determine whether interferon beta-1a could slow the progressive, irreversible, neurological disability of relapsing multiple sclerosis. Three hundred one patients with relapsing multiple sclerosis were randomized into a double-blinded, placebo-controlled, multicenter phase III trial of interferon beta-1a. Interferon beta-1a, 6.0 million units (30 micrograms¿, was administered by intramuscular injection weekly. The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Expanded Disability Status Scale (EDSS). Interferon beta-1a treatment produced a significant delay in time to sustained EDSS progression (p = 0.02). The Kaplan-Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9% in the placebo group and 21.9% in the interferon beta-1a-treated group. Patients treated with interferon beta-1a also had significantly fewer exacerbations (p = 0.03) and a significantly lower number and volume of gadolinium-enhanced brain lesions on magnetic resonance images (p-values ranging between 0.02 and 0.05). Over 2 years, the annual exacerbation rate was 0.90 in placebo-treated patients versus 0.61 in interferon beta-1a-treated patients. There were no major adverse events related to treatment. Interferon beta-1a had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium-enhanced lesions on brain magnetic resonance images. This treatment may alter the fundamental course of relapsing multiple sclerosis.

Abstract The Hopkins Verbal Learning Test (HVLT) is a brief verbal learning and memory test with six alternate forms. The HVLT is ideal in situations calling for repeated neuropsychological examinations, but it lacks a delayed recall trial which is essential for the assessment of abnormal forgetting. We present a revised version of the HVLT which includes a delayed recall trial, and therefore delays the yes/no recognition trial. The equivalence of test forms was examined in two separate studies using between-groups and within-subjects research designs. In both studies, the six forms of the revised HVLT (HVLT-R) were found to be equivalent with respect to the recall trials, but there were some modest differences in recognition. Recommendations for the use of the HVLT-R in serial neuropsychological examinations are provided, as well as normative data tables from a sample of 541 subjects, spanning ages 17 to 88 years.

BACKGROUND: Right ventricular pacing restores an adequate heart rate in patients with atrioventricular block, but high percentages of right ventricular apical pacing may promote left ventricular systolic dysfunction. We evaluated whether biventricular pacing might reduce mortality, morbidity, and adverse left ventricular remodeling in such patients. METHODS: We enrolled patients who had indications for pacing with atrioventricular block; New York Heart Association (NYHA) class I, II, or III heart failure; and a left ventricular ejection fraction of 50% or less. Patients received a cardiac-resynchronization pacemaker or implantable cardioverter-defibrillator (ICD) (the latter if the patient had an indication for defibrillation therapy) and were randomly assigned to standard right ventricular pacing or biventricular pacing. The primary outcome was the time to death from any cause, an urgent care visit for heart failure that required intravenous therapy, or a 15% or more increase in the left ventricular end-systolic volume index. RESULTS: Of 918 patients enrolled, 691 underwent randomization and were followed for an average of 37 months. The primary outcome occurred in 190 of 342 patients (55.6%) in the right-ventricular-pacing group, as compared with 160 of 349 (45.8%) in the biventricular-pacing group. Patients randomly assigned to biventricular pacing had a significantly lower incidence of the primary outcome over time than did those assigned to right ventricular pacing (hazard ratio, 0.74; 95% credible interval, 0.60 to 0.90); results were similar in the pacemaker and ICD groups. Left ventricular lead-related complications occurred in 6.4% of patients. CONCLUSIONS: Biventricular pacing was superior to conventional right ventricular pacing in patients with atrioventricular block and left ventricular systolic dysfunction with NYHA class I, II, or III heart failure. (Funded by Medtronic; BLOCK HF ClinicalTrials.gov number, NCT00267098.).

Cognitive and motor performance measures are commonly employed in multiple sclerosis (MS) research, particularly when the purpose is to determine the efficacy of treatment. The increasing focus of new therapies on slowing progression or reversing neurological disability makes the utilization of sensitive, reproducible, and valid measures essential. Processing speed is a basic elemental cognitive function that likely influences downstream processes such as memory. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. Among the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step for these neuroperformance metrics is elucidation of clinically relevant benchmarks, well-defined degrees of disability, and gradients of change that are deemed clinically meaningful. This topical review provides an overview of research on one particular cognitive measure, the Symbol Digit Modalities Test (SDMT), recognized as being particularly sensitive to slowed processing of information that is commonly seen in MS. The research in MS clearly supports the reliability and validity of this test and recently has supported a responder definition of SDMT change approximating 4 points or 10% in magnitude.

PURPOSE: To (1) identify greatest 6-minute walk distance (6MWD) from among several repetitions (best 6MWD) in a wide age range of healthy volunteers to develop reference values for the multiple repetition 6MWD, and (2) investigate the influence of demographics, anthropometrics, and habitual exercise activity on best 6MWD. METHODS: Four 6MWD were performed on the same day in a 20-meter corridor by 41 male and 38 female healthy volunteers ranging in age from 20 to 80 years. The greatest 6MWD by each subject from among four 6MWDs was the primary outcome measure. RESULTS: Eighty-six percent had their best 6MWD after the first walk; an average increase of 43 meters was observed from first to best 6MWD (P < 0.003). Best 6MWD averaged 698 +/- 96 meters and was inversely related to age (P < 0.001), directly to height (P < 0.001), and was greater in men than women (P < 0.0002). A regression model accounted for 41% of between-subject variability in best 6MWD (P < 0.00000001). In a subset of older subjects, predicted 6MWD significantly underestimated measured best 6MWD when reference values were used from another study where test familiarization was not provided, but this difference disappeared when value were used from the present and a third study where test familiarization was provided. CONCLUSIONS: The present study is the first to provide predicted 6MWD values performed with multiple repetitions and for subjects in the 20-40-year-old age range. Selection of appropriate predicted 6MWD values for interpretation of performance should be guided by subject age and degree of test familiarization provided.

One-plane cineangiographic measurement of left ventricular volume uses angiocardiograms taken in the right anterior oblique view. Its basic assumption is that the third (unvisualized) dimension, depth from septum to free wall, is of the same magnitude and behaves in the same way as the visualized short axis. Examination of this assumption with biplane x-ray equipment revealed that the unmeasured length averages 7% less and varies directly with the length of the measured short axis. Volumes measured correlate well with consecutive studies using serial biplane x-rays and are systematically somewhat larger than volumes obtained in autopsy specimens injected with barium sulfate paste. The method is tolerant of variations in positioning of the patient, is convenient, yields repeatable analyses from one experienced observer to another, allows 60 volume measurements per second so that rapid cardiac events can be studied, and the small doses of x-rays and contrast medium permit several observations at one catheterization session. This means that effects of drugs and other interventions can be studied by the informative techniques of semi-continuous volume measurement and pressure-volume analysis.

Background: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. Methods: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0–2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. Results: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( P &lt;0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06–1.79; P =0.02). Likewise, excellent outcome (modified Rankin Score 0–1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13–1.92; P =0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P =0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. Conclusions: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.

An international expert consensus committee recently recommended a brief battery of tests for cognitive evaluation in multiple sclerosis. The Brief International Cognitive Assessment for MS (BICAMS) battery includes tests of mental processing speed and memory. Recognizing that resources for validation will vary internationally, the committee identified validation priorities, to facilitate international acceptance of BICAMS. Practical matters pertaining to implementation across different languages and countries were discussed. Five steps to achieve optimal psychometric validation were proposed. In Step 1, test stimuli should be standardized for the target culture or language under consideration. In Step 2, examiner instructions must be standardized and translated, including all information from manuals necessary for administration and interpretation. In Step 3, samples of at least 65 healthy persons should be studied for normalization, matched to patients on demographics such as age, gender and education. The objective of Step 4 is test-retest reliability, which can be investigated in a small sample of MS and/or healthy volunteers over 1-3 weeks. Finally, in Step 5, criterion validity should be established by comparing MS and healthy controls. At this time, preliminary studies are underway in a number of countries as we move forward with this international assessment tool for cognition in MS.

The purpose of this study was to investigate disability in persons with multiple sclerosis (MS) by using combinations of functional assessment scales and subscales to predict (1) the burden of care measured in minutes of assistance provided per day by another person in the home, and (2) the subject's level of satisfaction with life in general. The Functional Independence Measure (FIM), Incapacity Status Scale, Environmental Status Scale, and the Barthel Index had high intercorrelations with each other. Although each was predictive of the MS subject's physical care needs, the FIM was the most useful. A change in total FIM score of one point was equivalent to an average of 3.38 minutes of help from another person per day. With the Brief Symptom Inventory and the Environmental Status Scale, the FIM contributed to predicting the patient's general satisfaction as well. We propose that burden of care and subjective satisfaction with life be the standards by which functional assessment instruments are compared to reflect, in pragmatic terms, the impact of disability on the lives of individuals and on the human and economic resources of the community.

The Multiple Sclerosis Collaborative Research Group trial was a double-blind, randomized, multicenter, phase III, placebo-controlled study of interferon beta-1a (IFNbeta-1a; AVONEX) in relapsing forms of multiple sclerosis. Initial magnetic resonance imaging results have been published; this report provides additional results. Treatment with IFNbeta-1a, 30 microg once weekly by intramuscular injection, resulted in a significant decrease in the number of new, enlarging, and new plus enlarging T2 lesions over 2 years. The median increase in T2 lesion volume in placebo and IFNbeta-1a patients was 455 and 152 mm3, respectively, at 1 year and 1,410 and 628 mm3 at 2 years, although the treatment group differences did not reach statistical significance. For active patients, defined as those with gadolinium enhancement at baseline, the median change in T2 lesion volume in placebo and IFNbeta-1a patients was 1,578 and -12 mm3 and 2,980 and 1,285 mm3 at 1 and 2 years, respectively. Except for a minimal correlation of 0.30 between relapse rate and the number of gadolinium-enhanced lesions, correlations between MR and clinical measures at baseline and throughout the study were in general poor. Once weekly intramuscular IFNbeta-1a appears to impede the development of multiple sclerosis lesions at an early stage and has a favorable impact on the long-term sequelae of these inflammatory events as indicated by the slowed accumulation of T2 lesions.

Gradual distension of the knee joint with plasma was observed to result in weakening of the quadriceps muscle in sixteen subjects. In normal subjects this occurred before pain was experienced, but in some subjects with articular disease, particularly rheumatoid arthritis, pain preceded weakness of the quadriceps. In a patient with neuropathic disease of the knee joint muscle weakness did not develop even when the joint was distended at high pressure. Similarly, in other subjects, the instillation of local anesthetics delayed the appearance of weakness until the joints were distended at higher pressures. These studies suggest that stimuli from the knee joint reflexly inhibit the lower motoneurons supplying the quadriceps muscle. Reflex inhibition may lead to the muscle weakness, the atrophy, and the deformity that are seen in association with joint disease.

Cognitive dysfunction is common in multiple sclerosis (MS), yet few studies have examined effects of treatment on neuropsychological (NP) performance. To evaluate the effects of interferon β-1a (IFNβ-1a, 30 μg administered intramuscularly once weekly [Avonex]) on cognitive function, a Comprehensive NP Battery was administered at baseline and week 104 to relapsing MS patients in the phase III study, 166 of whom completed both assessments. A Brief NP Battery was also administered at 6-month intervals. The primary NP outcome measure was 2-year change on the Comprehensive NP Battery, grouped into domains of information processing and learning/memory (set A), visuospatial abilities and problem solving (set B), and verbal abilities and attention span (set C). NP effects were most pronounced in cognitive domains vulnerable to MS: IFNβ-1a had a significant beneficial effect on the set A composite, with a favorable trend evident on set B. Secondary outcome analyses revealed significant between-group differences in slopes for Brief NP Battery performance and time to sustained deterioration in a Paced Auditory Serial Addition Test processing rate, favoring the IFNβ-1a group. These results support and extend previous observations of significant beneficial effects of IFNβ-1a for relapsing MS. Ann Neurol 2000;48:885–892

OBJECTIVE: The study sought to determine if there were race/ethnicity or gender differences in access to coronary artery bypass graft (CABG) surgery among patients who have been designated as appropriate and as necessary for that surgery according to the RAND methodology. METHODS: RAND appropriateness and necessity criteria were used to identify a race/gender stratified sample of postangiography patients who would benefit from coronary artery bypass graft surgery. These patients were tracked for 3 months to determine if they had undergone coronary artery bypass graft surgery in New York State. Subjects were a total of 1,261 postangiography patients in eight New York hospitals in 1994 to 1996. Measures included percentages of patients for whom coronary artery bypass graft surgery was appropriate and necessary undergoing surgery by race/ethnicity and gender, as well as multivariate odds ratios for race/ethnicity and gender. RESULTS: After controlling for age, payer, number of vessels diseased, and presence of left main disease, African-American and Hispanic patients were found to be significantly less likely to undergo coronary artery bypass graft surgery than white non-Hispanic patients (respective odds ratios 0.64 and 0.60). When "necessity" was used as a criterion instead of "appropriateness," significant differences in access for African-American patients remained. The gatekeeper physician recommended surgery only 10% of the time that patients did not undergo "appropriate" coronary artery bypass graft surgery, and this percentage did not vary significantly by race/ethnicity or gender of the patient. CONCLUSIONS: Even after controlling for appropriateness and necessity for coronary artery bypass graft surgery in a prospective study, African-American patients had significant access problems in obtaining coronary artery bypass graft surgery. These problems appeared not to be related to patient refusals.

It is unclear whether brain MRI lesions are associated with depression in multiple sclerosis (MS). Neurological dysfunction in depressed (n= 19) and non-depressed (n = 29) MS patients was rated by expanded disability status scale (EDSS). EDSS was weakly predictive of the presence of (p = 0.03) and severity of (p = 0.01) depression. After correcting for EDSS, the presence of depression was predicted by superior frontal and superior parietal hypointense TI lesions (p<0.01); the severity of depression was predicted by superior frontal, superior parietal and temporal TI lesions, lateral and third ventricular enlargement, and frontal atrophy (p<0.01). Depression was not related to bright T2 lesions or enhancement. We conclude that atrophy and cortical-subcortical disconnection due to frontal and parietal white matter destructive lesions may contribute to depression in MS.

BACKGROUND: Autopsy studies showed cortical and juxtacortical multiple sclerosis (MS) plaques. Fluid-attenuated inversion recovery (FLAIR) is an advanced magnetic resonance imaging sequence that reveals tissue T2 prolongation with cerebrospinal fluid suppression, allowing detection of superficial brain lesions. OBJECTIVES: To assess FLAIR, T1-weighted, and T2-weighted images for detecting lesions in or near the cerebral cortex in patients with MS and to explore the relation between cortical lesions and cortical atrophy. DESIGN, SETTING, AND PATIENTS: Cross-sectional study in a university MS clinic of 84 patients with MS and 66 age-matched healthy controls receiving 1.5-T fast FLAIR, T2-weighted, and T1-weighted images. MAIN OUTCOME MEASURES: Regional cortical atrophy was rated vs controls. Cortical and juxtacortical lesions were ovoid hyperintensities involving the cortex and/or gray-white junction. RESULTS: A total of 810 cortical and juxtacortical lesions were seen by FLAIR in patients (mean, 9.6 per patient), most commonly in the superior frontal lobe. Cortical and juxtacortical lesions were identified in 72 patients and 6 controls. Fourteen percent of cortical and juxtacortical lesions were seen on T1-weighted images and 26% were seen on T2-weighted images. More cortical and juxtacortical lesions were present in secondary progressive disease than relapsing-remitting disease. The total number of cortical and juxtacortical lesions correlated significantly with disease duration and the regional number correlated with the degree of regional atrophy. After taking into account noncortical (white matter) lesions, only the cortical and juxtacortical lesion count predicted atrophy in that region. CONCLUSIONS: FLAIR can detect many cortical and juxtacortical lesions in MS, which were appreciated previously in autopsy studies but usually missed by magnetic resonance imaging during life. Cortical and juxtacortical plaque formation may contribute to cortical atrophy in MS.

The efficacy of three operative approaches to the cavernous sinus (CS) and the possibilities of vascular and cranial nerve reconstruction in and around the CS were studied in 50 cadaver specimens (25 heads). The lateral operative approach was through the lateral wall, between Cranial Nerves V1 and IV, or between Cranial Nerves V1 and V2. The superior approach was through the superior wall of the CS after removing the anterior clinoid process and unroofing the optic canal. The inferior approach followed the petrous internal carotid artery (ICA) into the CS after an extradural subtemporal exposure or after a combined subtemporal and infratemporal fossa exposure. The different exposures of the spaces of the CS and of the intracavernous structures provided by the superior and the lateral approaches were complementary. The exposure provided by the inferior approach was minimal; however, the junction of the petrous and cavernous ICA was best exposed by this route. The combined subtemporal and infratemporal fossa approach exposed the petrous ICA (for proximal control or for reconstruction) with the greatest ease and with the least temporal lobe retraction. The combination of the superior and lateral approaches and the complete mobilization of the intracavernous ICA facilitated its repair after experimental lacerations. Lacerations of either the inferior and the inferomedial aspects of any portion of the cavernous ICA or of the anterior surface of the posterior vertical segment of the artery were the most difficult to repair. End-to-end anastomosis was more difficult with the posterior third of the artery than with the anterior two-thirds. A vein graft with an average length of 3.5 cm could be sutured from the petrous to the supraclinoid ICA to bypass the cavernous ICA, with an average occlusion time of 45 minutes. End-to-end technique was judged better for the proximal anastomosis, but end (graft)-to-side anastomosis was easier to perform at the distal end because of the location of the ophthalmic artery. Resuture of Cranial Nerves III and VI could not be performed in fresh cadavers if the gap exceeded 0.3 cm. In 3 specimens, the exposure of Cranial Nerve VI in the posterior fossa through the petrous apex and in the orbital apex was followed by graft placement (bypassing the CS). The complex anatomy of the cranial nerves at the apex of the CS was also defined in 10 specimens. Surgeons who perform operations in and around the CS for neoplastic and vascular lesions will find these studies useful.

Summary Crude saline extracts of rabbit thyroids proved to be antigenic for rabbits. The technique of immunization consisted of the intradermal injection of 0.05 ml of a mixture of tissue extract plus Freund adjuvants into each of the 4 footpads in the rabbit. The percentage of rabbits showing circulating antibodies varied from experiment to experiment. Rabbit thyroid antibodies were demonstrated by complement fixation and precipitation techniques. In addition, erythrocytes tanned according to Boyden’s procedure and coated with thyroid extracts provided a sensitive tool for the demonstration of rabbit thyroid antibodies in high antiserum dilution. The thyroid antibodies are tissue-specific rather than group-specific, reacting with the thyroid extracts of any rabbit tested regardless of whether the rabbit itself produced thyroid antibodies or failed to do so. Thyroidectomized, or partially thyroidectomized, rabbits injected with extracts of their own thyroid glands produced antibodies reacting with their own thyroid extracts as well as with thyroid extracts of any other rabbit tested.

Brain atrophy measurement can provide an estimate of the amount of tissue destruction due to the pathologic processes in multiple sclerosis. The potential usefulness of atrophy as a marker of disease progression depends upon the concurrent and predictive relationships between atrophy and disability. A follow-up study was performed to measure atrophy and disability scores in patients from the Multiple Sclerosis Collaborative Research Group's phase III trial of IFNbeta-1a (Avonex) in relapsing- remitting multiple sclerosis. New data were obtained on 160 out of 172 eligible patients from the original trial were enrolled in the follow-up study approximately 8 years after randomization. The follow-up visit consisted of several tests and questionnaires including a clinical exam to determine Expanded Disability Status Score (EDSS) and Multiple Sclerosis Functional Composite (MSFC), and a magnetic resonance imaging exam to calculate the brain parenchymal fraction. Brain parenchymal fraction was correlated with both EDSS and MSFC at each of the four time points for which data were available (baseline 1, 2 and 8 years). Furthermore, the change in BPF was correlated with the changes in disability scores from the end of the phase III trial to the follow-up exam. These data suggest that brain atrophy may be a useful and clinically relevant marker of disease progression in relapsing--remitting MS.

A prospective trial from July 1976 to September 1980 by the National Prostatic Cancer Project randomized newly diagnosed metastatic prostate cancer patients to DES 1 mg orally three times daily or orchiectomy; or DES, 1 mg, three times daily, plus cyclophosphamide at 1 mg/m2 iv every three weeks, or cyclophosphamide 1 g/m2 iv every three weeks plus estramustine phosphate (Estracyt) at 600 mg/m2 orally daily in three divided doses. There were 246 patients evaluated for response of 301 entered. These consisted of 83 on the DES/orchiectomy arm, 77 on DES plus cyclophosphamide, and 86 on Estracyt plus cyclophosphamide. Objective response rates, initially evaluated at 12 weeks, were similar among the treatments. However, chemotherapy as used in this study early in the diagnosis of metastatic disease appears to exhibit an improved effect on overall survival compared to hormone therapy alone. Analysis within groups having pain versus no pain at entry revealed a marked advantage after 80 weeks for chemotherapy when pain was initially present and a slight advantage during treatment (throughout follow-up) when the pain was absent. Median survival times were 92, 91, and 94 weeks, respectively, for the three treatments. The progression-free interval for responders showed no difference between initial treatments, although nearly one half of the patients are still in remission; hence, further follow-up will be essential. Side effects were not excessive for the chemotherapy treatment arms and patient compliance was good. This national multicenter trial provides the basis for further testing of chemotherapy agents at an earlier phase for patients with newly diagnosed metastatic prostate cancer.

Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, alpha(1)-acid-glycoprotein (AAG), alpha(1)-antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P = 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P = 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P = 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P = 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.