RESPONSIVENESS OF KEITEL FUNCTIONAL INDEX COMPARED WITH LABORATORY MEASURES OF DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS

This study compares functional changes to change in measuresof disease activity following the introduction of slow-actinganti-rheumatic drugs (SAARD) in patients with active rheumatoidarthritis (RA). Clinical and laboratory variables were simultaneouslymonitored at 6-monthly intervals, over approximately 18 months.Function was measured by a performance testing, the Keitel functionindex (KFI), which was divided into sections representing smalland large joints [and (HFI); wrist (WFI) and limb function index(LFI)]. One-hundred-and-fifteen patients were studied, of whom21 were male. The mean age of the subjects was 49 yr (s.D. ±12) and mean duration of disease 7 yr (S.D. ± 7). Themean KFI at entry was 38 (S.D. ± 18) while at the endof the study it was 31 (s.D. ± 17) (P < 0.0001). Thechange in KFI following therapy correlated with the change inRitchie articular index (RAI) (r = 0.4; P < 0.0001), earlymorning stiffness (EMS) (r = 0.3; P = 0.004), swollen jointcount (JC) (r = 0.4; P = 0.0005). C-reactive protein (CRP) (r= 0.2; P < 0.05) and Lansbury systemic index (LSI) (r = 0.35;P = 0.002), but not with change in Westergren erythrocyte sedimentationrate (ESR) or change in time to onset of fatigue. Multiple regressionanalysis showed that 32% of the variation in KFI at the endof the study could be predicted by a combination of ESR, sulphasalazinetherapy, RAI, disease duration and chloroquine treatment atonset (P < 0.05). When HFI at end of study was the dependentvariable, 21 % of the variation could be predicted by a combinationof ESR, CRP, Lansbury systemic index and JC at onset (P <0.05). The duration of disease did not significantly influencethe potential for change in functional status. This study showedthat detailed measurement of function is important in assessingRA activity. Functional impairment in RA is a dynamic processinfluenced by changes in clinical disease activity with treatment. KEY WORDS: Keitel function index, Disease activity, Outcom, Hand function index     

Are activity indices helpful in assessing active intestinal inflammation in Crohn's disease?

We have investigated the correlation of 24 h and 48 h faecal Indium-111 excretion with each other and with several clinical activity indices for Crohn's disease (CD): Crohn's disease activity index (CDAI), activity index (AI), simple index (SI), Oxford score, and laboratory parameters, such as ESR, serum albumin, orosomucoid, C-reactive protein, alpha-l-antitrypsin (alpha 1-AT) faecal concentration, and alpha 1-AT clearance in 58 CD patients (37 with small bowel and 21 with colonic disease). A significant correlation was found between 24 and 48 h faecal Indium-111 excretion for small bowel (r = 0.708, p less than 0.0001) and colonic disease (r = 0.994, p less than 0.0001). The median faecal Indium-111 excretion for colonic involvement (4%; 0.15-50% median and range) was significantly (p less than 0.005) higher than that for small bowel disease (0.45%; 0.03-2.9%). No significant correlation was found between faecal Indium-111 excretion and any activity index in the patients with small bowel disease, while in the group of patients with colonic localisation only the AI showed a significant correlation (r = 0.593, p less than 0.02). Faecal Indium-111 excretion was significantly correlated with alpha 1-AT clearance (r = 0.712, p less than 0.0001) and faecal alpha 1-AT concentration (r = 0.750, p less than 0.0001) in small bowel and in colonic localisation (r = 0.530, p less than 0.02 and r = 0.444, p less than 0.05). Serum albumin was significantly correlated only in the group of patients with colonic disease (r = -0.593, p less than 0.05). The present study shows poor agreement between activity indices, serum parameters of activity and faecal Indium-111 excretion. As a good correlation was found with the alpha1-clearance, which reflects losses into the gut, these results may suggest that faecal Indium excretion does not only reflect activity of inflammation, but my relate to the extent of intestinal ulceration.     

Increased type I collagen degradation correlates with disease severity in rheumatoid arthritis.

OBJECTIVES--To assess the extent and clinical significance of type I collagen degradation in rheumatoid arthritis (RA). METHODS--Serum samples from 90 consecutive patients with RA from a cross-sectional population based study and 90 age- and sex-matched controls were analysed with the new assay of cross-linked carboxyterminal telopeptide of type I collagen (ICTP). RESULTS--Patients with RA had significantly higher concentrations of ICTP than the controls. ICTP correlated strongly with measures of impairment in RA, such as the erosive state of joint disease (ES) (r = 0.57, p < 0.001) and Keitel function test (KFT) (r = 0.49, p < 0.001), and more weakly with various disease activity markers. When erythrocyte sedimentation rate (ESR), ES or KFT were used as indicators of disease severity among the patients with disease duration over five years, ICTP distinguished the more serious RA from milder cases. CONCLUSIONS--Elevated serum concentrations of ICTP are common in RA and are associated with signs of aggressive disease.     

In vitro migration of mononuclear cells towards synovial fluid and plasma from rheumatoid arthritis patients correlates to RANTES synovial fluid levels and to clinical pain parameters

OBJECTIVE: To evaluate in vitro migration of mononuclear cells towards synovial fluid (SF) and plasma in relation to RANTES synovial fluid levels and clinical disease activity. METHODS: 31 RA patients with synovitis in one knee were included. Modified Boyden chamber technique was used to determine a migratory index defined as: 'In vitro migrating cells towards SF' divided by 'In vitro migrating cells towards plasma'. RANTES was quantified by ELISA. Disease activity was assessed by the swollen joint count, the Ritchie articular index (RAI), global assessment, pain on VAS, HAQ, ESR and CRP. RESULTS: A positive significant correlation was found between the migratory index and the RANTES levels in SF (r=0.48, p=0.006), the RAI (r=0.56, p=0.0001) and pain on VAS (r=0.43, p=0.04). The in vitro migration could be inhibited in 3 of 4 SF samples by neutralising antibodies towards RANTES (12-18%). CONCLUSION: The migratory index correlate to SF levels of RANTES and parameters for joint pain.     

Measurement of hand bone mineral content by dual energy x-ray absorptiometry: development of the method, and its application in normal volunteers and in patients with rheumatoid arthritis.

OBJECTIVES--To develop a method of measuring hand bone mineral content (BMC) by dual energy x ray absorptiometry (DXA); to apply this method of measuring hand BMC to normal volunteers to ascertain causes of variability; and to measure hand BMC in patients with rheumatoid arthritis (RA) of varying duration and severity. METHODS--The x ray beam of the Hologic QDR 1000 dual energy x ray absorptiometer was hardened by introducing a perspex-aluminium plate and the analysis software altered to allow for the small tissue bulk of the hand compared with the torso. Ninety five volunteers (46 men age 24-81 and 49 women age 20-83) had scans of both hands. Eight volunteers were assessed repeatedly to establish reproducibility and effect of hand position. Fifty six patients (22 men, 34 women, age range 25-86 years) with RA of differing duration and severity, had hand BMC measurement by DXA. RESULTS--The precision of BMC measurement was 2.3% with no additional variation due to hand position. Hand dominance had no significant effect on BMC. In men, hand BMC correlated with height (r = 0.57, p < 0.0001), weight (r = 0.58, p < 0.0001), forearm span (r = 0.5, p = 0.0006) and hand volume (r = 0.66, p < 0.0001). In women hand BMC correlated with height (r = 0.66, p < 0.0001), weight (r = 0.4, p = 0.003), forearm span (r = 0.3, p = 0.03) and hand volume (r = 0.49, p = 0.0008). After correcting for all these variables, male volunteers had significantly higher hand BMC than female volunteers (p = 0.01) and patients with RA had lower hand BMC than normal volunteers (total hand BMC in male volunteers 90.9 gms, 95% CI 86.9-95, in male patients 81.7 gms, 95% CI 73.7-89.6, p < 0.004, total hand BMC in female volunteers 62.2 gms 95% CI 59.8-64.5, female patients 52.3 gms, 95% CI 48.1-56.5, p < 0.005). In patients with RA, the hand BMC showed an inverse correlation with age (r = -0.44, p = 0.01), disease duration (r = -0.62, p = 0.0003), Larsen's grades (r = -0.62, p = 0.0002) and modified Sharp's method score (r = -0.69, p < 0.0001) in female patients only. CONCLUSIONS--A new, sensitive and reproducible technique of measurement of hand bone mineral content by DXA, has been developed and this method has been applied to normal volunteers and patients with RA. Hand dominance had no significant effect on hand BMC. After correcting for physical size, men have higher hand BMC than women. Hand BMC inversely correlates in women patients with disease duration and other validated methods of assessing radiological outcome in RA. Longitudinal studies are needed to establish its role in monitoring disease progression.     

Changes in modalities of left ventricular filling associated with aging in normal subjects: secondary to increase in blood pressure and left ventricular mass?

The mechanisms by which aging alters the pattern of left ventricular diastolic filling are still uncertain. To gain more insight into this tissue, the independent contributions of age, sex, heart rate, arterial blood pressure and left ventricular mass (as well as various indexes of left ventricular morphology and function) to left ventricular diastolic filling abnormalities, were investigated by echocardiography in 81 normal subjects (18 to 84 years of age, mean 50), carefully screened to avoid the confounding effects of coronary artery disease and systemic hypertension. With advancing adult age, we found a significant increase in: body mass index (r = 0.25; p less than 0.02), systolic (r = 0.58; p less than 0.0001), pulse (r = 0.61; p less than 0.0001) and mean (r = 0.40; p less than 0.0001) arterial blood pressure; left ventricular wall thickness (r = 0.30; p less than 0.006); left ventricular mass (r = 0.32; p less than 0.004); left ventricular end-diastolic volume (r = 0.24; p less than 0.03); and peak systolic wall stress (r = 0.22; p less than 0.04). Pulsed Doppler analysis of mitral inflow showed a significant age-related decline in the peak early filling velocity (r = -0.51; p less than 0.001), and in the ratio of early and late diastolic filling velocity (r = -0.65; p less than 0.0001). Conversely, duration of isovolumic relaxation (r = 0.77; p less than 0.0001), peak late diastolic flow velocity (r = 0.39; p less than 0.001), and diastolic pressure half time (r = 0.34; p less than 0.01) increased significantly with age. "Stepwise" multivariate linear regression analyses showed that the ratio of early to late diastolic peak filling velocity was independently related only with age (R2 = 0.56; p less than 0.0001) while the isovolumic relaxation time was independently related with age (R2 = 0.48; p less than 0.0001) and duration of cardiac cycle (R2 = 0.06; p less than 0.008). Age-related changes in body mass index, blood pressure, peak meridional wall stress and left ventricular mass index did not show any independent relationship to Doppler parameters of left ventricular filling or duration of isovolumic relaxation. The results of the present study suggest that the effect of age on left ventricular filling modalities and duration of isovolumic relaxation are independent of age-related changes in blood pressure, left ventricular mass, morphology and systolic function.     

Relationship between urinary sialylated saccharides, serum amyloid A protein, and C-reactive protein in rheumatoid arthritis and systemic lupus erythematosus.

The urinary excretion of sialic-acid-containing oligosaccharides, total sialic acid, serum amyloid A protein (SAA), and C-reactive protein (CRP) has been studied in 48 patients with rheumatoid arthritis (RA) and in 17 patients with systemic lupus erythematosus (SLE). Linear regression analysis revealed a close positive correlation between serum SAA and CRP levels in both RA (r = 0.71, p less than 0.001) and SLE (r = 0.86, p less than 0.001). The urinary excretion of sialyl lactose showed a positive correlation with the serum levels of SAA and CRP in RA (r = 0.45 and r = 0.45, respectively, p less than 0.01) but not in SLE (r = 0.05 and r = 0.10 respectively). Changes in serum total sialic acid levels paralleled those in CRP and SAA in RA as well as in SLE. Patients with very active RA had higher urinary sialyl oligosaccharide excretion (p less than 0.001), higher CRP levels (p less than 0.01), and higher SAA levels ( p less than 0.05) than those with moderately active disease.     

"5D" Outcome in 52 patients with rheumatoid arthritis surviving 20 years after initial disease modifying antirheumatic drug therapy

OBJECTIVE: Evaluation of a complex and variable disease such as rheumatoid arthritis (RA) poses a challenge particularly over the medium to long term. A practical framework to evaluate clinically relevant outcomes over the long term is the "5D" approach of Fries, described in 1980. We describe the 20 year outcome in 52 survivors of a 123 patient cohort in terms of change in discomfort, disability, drug side effects, dollar costs, and deaths. METHODS: We studied 123 patients with RA allocated to their first disease modifying antirheumatic drug (DMARD) between 1977 and 1979. All were under the overall care of one physician over the 20 years and were maintained where possible taking a single DMARD. Baseline demographic variables, the Ritchie Articular Index (RAI), Lee functional index, and erythrocyte sedimentation rate (ESR) were initially recorded. The extent to which the demographic and disease variables contributed to need for joint replacement surgery was assessed. Therapies for comorbidity were also documented. RESULTS: At cohort inception mean age was 50 years, RAI was 35, and median disease duration 5.5 years. F:M ratio was 90:33; 96% of patients were positive for rheumatoid factor (RF). Initial median ESR was 55 mm/h. At 20 years, 9 patients (7% of original cohort, 14% of survivors) were lost to followup and 62 (50%) had died. In the 52 survivors RAI, a surrogate for disability, showed a significant improvement (p < 0.0001), but disability measured by Lee functional index showed a deterioration (p = 0.018); 50% underwent joint replacement surgery. Initial ESR and mean ESR over the first 10 years of followup were significantly higher in those who required surgery. Nonsteroidal antiinflammatory drug (NSAID) use declined, but at least 2 deaths and 4 renal deaths that may have been related to therapy were attributed to NSAID use. No unexpected DMARD toxicity or mortality occurred. Concomitant therapy for comorbidity, in particular for cardiovascular disease, osteoporosis, and gastrointestinal disease, increased: more than 60% were on these therapies at 20 year followup. CONCLUSION: Strategies to improve the outcome of RA in all dimensions should include: earlier referral for expert assessment; avoidance of NSAID gastrointestinal and nephrotoxicity; a more intensive effort to identify effective management of comorbidity and those likely to have a poor outcome. Such patients require sustained, intensive therapy to minimize later disability.     

Biventricular functional adaptation during a prolonged race. An analysis of global and regional ventricular function]

To determine the effects of a six-hour competitive race on left and right ventricular performance, 99mTc gated blood pool scans were performed to 6 long distance runners before the race (rest), each hour during the race and one hour after concluding the exercise (recovery). Heart rate increased during the race, peaking at 4th hour of competition (55 +/- 3 to 110 +/- 9 lpm; p = 0.001). Evolution of right ventricular ejection fraction showed a similar behavior with the evolution of left ventricular ejection fraction during the competition (r = 0.39; p = 0.006). Blood volume in the lungs increased at the end of the race (index 1.13 +/- 0.14) normalizing at recovery (index 1.03 +/- 0.03). Left and right ventricular peak filling rate had an inverse correlation with pulmonary blood volume (r = -0.31; p = 0.041 and r = -0.47; p = 0.001 respectively). Both left and right ventricular ejection fraction had an inverse correlation with pulmonary blood volume (r = -0.38; p = 0.006 and r = -0.34; p = 0.01 respectively). The anteroseptal regional ejection fraction showed an inverse correlation with end-systolic and end-diastolic volume (r = -0.32; p = 0.03 and r = -0.4; p less than 0.01 respectively). The posterolateral region showed a parallel evolution with the global ejection fraction for both left and right ventricles (r = 0.57; p less than 0.0001 and r = 0.38; p = 0.009 respectively). In conclusion, a transient biventricular functional adaptation during a prolonged race is related to pulmonary blood volume redistribution and to a higher preload for both ventricles and a greater afterload for the right ventricle. The posterolateral and inferoapical regions show a similar behavior as both left and right ventricular ejection fraction, response that does not occur with the anteroseptal regional ejection fraction.     

Increased serum levels of interleukin-15 in rheumatoid arthritis with long- term disease

OBJECTIVE: To study the serum levels of IL-15 in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), seronegative spondyloarthropathies (SSd) and healthy donors. METHODS: The IL-15 serum levels were measured by ELISA in sera from 50 RA patients, 30 patients with SLE, 30 patients with SSd and 30 healthy donors. In RA patients, several clinical and demographic parameters were also obtained at the time of sample collection. IL-15 levels were compared in different RA subpopulations (positive or negative rheumatoid factor [RF], long term or recent onset disease, high or low disease activity). In addition, the possible association with other demographic and clinical parameters (gender, age, disease duration, etc) was also analysed. RESULTS: RA patients had significantly higher serum levels of IL-15 (102.4 +/- 150 pg/ml; p = 0.0001) than SLE patients (9.8 +/- 15.3 pg/ml), SSd patients (7.9 +/- 14.6 pg/ml) and healthy donors' (5.2 +/- 11.6 pg/ml). RA patients with a disease evolution less than 2 years showed lower IL-15 levels (33.7 +/- 62.2 pg/ml) than those with long-term disease (152.4 +/- 64.6 pg/ml; p = 0.004). In addition, a significant correlation between IL15 in serum and the number of disease-modifying antirheumatic drugs (DMARDs) prescribed was detected in RA patients (r = 0.42; p = 0.002). No association between IL-15 levels and age, gender, RF or disease activity was observed in this group. CONCLUSION: IL-15 is elevated in RA patients, specially in those with long term disease, compared to other rheumatic disorders. This finding supports that IL-15 is involved in the perpetuation of RA synovitis.     

Reversible volume changes of trapped gas in nonspecific bronchoprovocation tests.

Thirty patients with a history of asthma and ten patients with suspected bronchial hyperreactivity underwent nonspecific provocation testing. The control group consisted of ten normal volunteers without a history of lung disease. The patients' baseline FEV1 (percent predicted) revealed mild obstructive disease (72.9 +/- 8.9 percent and 74.6 +/- 7.7 percent) compared with controls (87.2 +/- 8.5 percent, p less than 0.001). The mean volume of trapped gas (D) (ie, TLCB-TLCHe) was not significantly different between groups (0.11 +/- 0.49 L vs 0.15 +/- 0.4 L vs 0.18 +/- 0.45 L), and no correlation was established with any of the remaining lung function data. Bronchial hyperreactivity in response to inhaling acetylcholine could be observed in the asthma group only. Their mean D increased significantly from 0.11 +/- 0.49 L to 0.62 +/- 0.66 L (p less than 0.001), and returned to baseline (0.26 +/- 0.55, NS) subsequent to inhaling salbutamol. D changes induced by acetylcholine correlated weakly with concurrent changes of FEV1 (r = -0.44, p = 0.01), RV (r = 0.59, p less than 0.001), and Rs (r = 0.59, p less than 0.001). In response to bronchodilating doses of salbutamol, however, D was changed in close correlation with FEV1 (r = -0.82, p less than 0.0001), RV (r = 0.85, p less than 0.0001), and Rs (r = 0.76, p less than 0.0001). Provided that D is a valid parameter of small airways function, these data may give a clue to the site of action of both drugs. Acetylcholine affects small and large airways alike with no clear-cut preference, whereas salbutamol's predominant target appears to be the small airways. These conclusions are only partially supported by the pertinent literature.     

Low number of complement C3b/C4b receptors (CR1) on erythrocytes from patients with essential mixed cryoglobulinemia, systemic lupus erythematosus and rheumatoid arthritis: relationship with disease activity, anticardiolipin antibodies, complement activation and therapy.

Our aim was to assess whether the amount of complement C3b/C4b receptors (CR1) on erythrocytes shows a correlation to disease activity in various connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and essential mixed cryoglobulinemia (EMC). Using an anti-CR1 monoclonal antibody, 26 patients with SLE, 34 with RA and 22 patients with EMC were investigated for erythrocyte CR1 expression. The control group consisted of 30 healthy individuals. The mean number of CR1/erythrocyte in the control group was 568 +/- 197 (range 174-1060), significantly higher than studied (EMC:379 +/- 248; p = 0.0005;SLE 147 +/- 56, p less than 0.0001; RA 298 +/- 177, p less than 0.0001). In patients with RA and in SLE, but not in patients with EMC, the number of CR1 numbers and anticardiolipin antibody (aCl) titers (r2 = 0.493; p = 0.034). A statistically significant correlation between CR1 numbers and CH50 values was found in patients with SLE, while in 3 patients with RA 4 months of therapy with cyclosporine A led to a further 30% reduction in CR1 number. Our conclusions are that (a) the decreased expression of erythrocyte CR1 is apparently a common feature of patients with various connective tissue diseases; (b) several acquired factors such as disease activity, complement activation, aCl and drugs may contribute to the loss of CR1 from erythrocytes; (c) in patients with RA and SLE, but not in patients with EMC, CR1 enumeration on erythrocytes may serve as a variable for clinical monitoring.     

Plasma monocyte chemoattractant protein 1 is a marker for joint inflammation in rheumatoid arthritis

OBJECTIVE: Monocyte chemoattractant protein 1 (MCP-1) level in plasma is described as a marker for joint inflammation in rheumatoid arthritis (RA). METHODS: MCP-1 in plasma and synovial fluid (SF) was quantified by ELISA in 36 RA patients with synovitis of the knee at Day 1 and 30. Disease activity was assessed by the swollen joint count, Ritchie Articular Index (RAI), global assessment, pain on visual analog scale, Health Assessment Questionnaire, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS: By linear regression analysis plasma MCP-1 levels correlated significantly with the swollen joint count (Day 1: R = 0.47, p = 0.005; Day 30: R = 0.53, p < 0.001) and the RAI (Day 1: R = 0.37, p = 0.03; Day 30: R = 0.41, p = 0.01). The correlations of swollen joint count and RAI with ESR and CRP were significant only on Day 30 for the ESR (R = 0.40, p = 0.02). No association was found between plasma MCP-1 levels and the ESR/CRP levels. MCP-1 levels in plasma in RA patients were elevated compared to controls (p < 0.001) and MCP-I levels in SF were higher than in plasma (p < 0.001). No correlation was found between SF MCP-1 levels and in vitro migration of mononuclear cells towards SF. MCP-1 appears to participate in the disease process in RA, and plasma MCP-1 may be useful in monitoring joint inflammation.     

Clinical and laboratory parameters which affect soluble interleukin-2 receptor levels in the serum and synovial fluids of patients with rheumatoid arthritis.

OBJECTIVE--To investigate whether soluble interleukin-2 receptor (sIL-2R) could be a useful marker of disease activity in rheumatoid arthritis (RA); sIL-2R levels in serum and in synovial fluid were determined by enzyme-linked immunosorbent assay. METHODS--Sixty five serum and 27 synovial fluid samples were obtained from patients with RA. Twenty five serum and 28 synovial fluid samples from patients with osteoarthritis (OA) were used as controls. Furthermore, 10 synovial fluid samples from healthy volunteers were also examined. Variable laboratory and clinical data were compared with serum sIL-2R levels, in 26 patients with RA and serial samples from some patients were examined. RESULTS--Concentrations of sIL-2R in serum (median 81, range 40-350 pM) and synovial fluid (median 125, range 52-460 pM) from patients with RA were significantly higher than in serum (median 45, range 13-100 pM) and synovial fluid (median 37, range 15-140 pM) from patients with OA, and healthy control synovial fluid (median 2.5, range 0-10 pM). Serum sIL-2R levels correlated strongly with serum levels of C-reactive protein (p = 0.0001), and a significant correlation with erythrocyte sedimentation rate (ESR) (p = 0.048), IgG levels (p = 0.028), IgA levels (p = 0.044) and Lansbury Index (p = 0.037) was observed. However, serum sIL-2R levels showed no significant correlation with rheumatic factor, IgM or T cell subsets. CONCLUSION--These findings indicate that sIL-2R levels in patients with RA reflect disease activity.     

Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings

To characterize the neural excitatory state of heart failure, simultaneous measurements of efferent sympathetic nerve activity to muscle (by microneurography) and rest hemodynamics were obtained in 10 normal subjects (age 25 +/- 2 years, mean +/- SEM) and 29 patients with heart failure (age 49 +/- 2 years; New York Heart Association functional class II to IV; left ventricular ejection fraction 21 +/- 1%; cardiac index = 2.16 +/- 0.13 liters/min per m2; pulmonary capillary wedge pressure 23 +/- 2 mm Hg). Sympathetic nerve activity was significantly higher in the patients with heart failure (54.7 +/- 4.5 bursts/min) than in normal subjects (16.7 +/- 2.2 bursts/min, p less than 0.001). Multiple linear regression analyses indicated that sympathetic activity in these human subjects was most strongly and inversely correlated with left ventricular stroke work index (r = -0.86, p less than 0.0001) and stroke volume index (r = -0.85, p less than 0.0001). There was a strong positive correlation between sympathetic nerve activity and pulmonary artery diastolic (r = 0.82, p less than 0.0001) and mean (r = 0.81, p less than 0.0001) pressures. Similar correlations were seen when patients with heart failure were analyzed separately. There was no significant correlation between sympathetic nerve activity and mean arterial pressure, left ventricular ejection fraction (by radionuclide ventriculography), cardiac chamber size (by echocardiography) or arterial oxygen tension in the patients with heart failure. Direct measurements of sympathetic nerve activity correlated closely with plasma norepinephrine (r = 0.72, p less than 0.0001) in patients with heart failure. Thus, sympathetic nerve activity at rest parallels impairment of cardiac performance in patients with heart failure.     

Serum matrix metalloproteinase 3 levels in comparison to C-reactive protein in periods with and without progression of radiological damage in patients with early rheumatoid arthritis

OBJECTIVE: To evaluate serum matrix metalloproteinase 3 (MMP-3) levels in comparison to C-reactive protein (CRP) in periods with and without progression of radiological damage in patients with early rheumatoid arthritis (RA). METHODS: Thirty-two patients with RA and radiological progression (> or = 5 points according to the Sharp/van der Heijde method) during 6 months followed by a 6-month period without radiological progression (< or = 1 point) were selected from a prospective follow-up study of early RA patients. Serum MMP-3 levels, CRP, the erythrocyte sedimentation rate (ESR), disease activity index (DAS), swollen joint count (SJC), tender joint count (TJC), and Ritchie articular index (RAI) were measured monthly and results were transformed into mean values for the 6-month periods. RESULTS: During the period with radiological progression the mean serum MMP-3 correlated significantly with the mean CRP (r = 0.68, p < 0.001), ESR (r = 0.54, p = 0.001) and swollen joint count (r = 0.48, p = 0.006). In the period without radiological progression the mean serum MMP-3 only correlated with the mean CRP (r = 0.44, p = 0.012). Individual changes--expressed in percentages (%)--between the two periods showed a decrease in both the mean serum MMP-3 and CRP in 19 and an increase in 3 patients, in parallel with other markers of disease activity in these patients (69% of cases). The individual change (%) in mean serum MMP-3 or CRP did not correlate with the difference in radiological progression between the two periods. CONCLUSIONS: Serum MMP-3 and CRP are closely related and there seems to be no difference between serum MMP-3 and CRP with regard to the monitoring of the progression of radiological damage.     

Elevated BAL fluid histamine levels and parenchymal pulmonary disease in rheumatoid arthritis

To determine the amount of histamine in BAL fluid in subjects with RA and to ascertain if elevated histamine levels were associated with parameters of active pulmonary disease, we measured BAL fluid histamine levels in 31 subjects with RA and 36 normal subjects. The subjects with RA had a significantly greater mean BAL histamine level than the normal subjects, (313 +/- 154 pg/ml vs 18 +/- 8 pg/ml; p less than 0.05). When the subjects with RA were divided into three groups based on chest radiograms (1 = normal; 2 = pleural disease only; 3 = interstitial or nodular disease), we found that subjects in group 3 had significantly lower values for TLC and D. Subjects in group 3 also had higher percentages of BAL neutrophils and eosinophils and higher BAL histamine levels (group 1, 115 +/- 52 pg/ml; group 2, 30 +/- 30 pg/ml; and group 3, 1,182 +/- 709 pg of histamine per milliliter). Moreover, BAL histamine levels were negatively correlated with TLC (r = -0.46; p = 0.01) and FVC (r = -0.45; p = 0.01) and positively correlated with BAL neutrophils (r = 0.6; p = 0.0003) and BAL eosinophils (r = 0.89; p = 0.0001). These data suggest that the BAL histamine level may be a useful marker to determine the activity of pulmonary disease in RA.     

Responsiveness of the Cochin rheumatoid hand disability scale after surgery

OBJECTIVE: To assess the responsiveness of the Cochin functional disability scale for the rheumatoid hand after surgery. METHOD: In a prospective study, patients with rheumatoid arthritis (RA) scheduled for surgery of the wrist and/or fingers were evaluated within 48 h before surgery and at least 6 months after surgery. Clinical outcome measures included duration of morning stiffness, total score for tenderness, total score for swelling, visual analogue scale score for pain in the hands and wrists, a score for overall mobility of the wrist and the fingers, grip and pinch strength, the Hand Functional Index (HFI), the Kapandji index and the Cochin scale. Responsiveness was assessed with the paired t-test, the effect size (ES), the standardized response mean (SRM) and the non-parametric Spearman rank correlation coefficient (r(S)). RESULTS: Fifty patients (42 women) were evaluated twice at an interval of 7.16 +/- 2.10 months (mean +/- s.d.) (range 6-15 months). Thirty-six patients (72%) were very satisfied or satisfied with the results of surgery, seven (14%) were not satisfied or dissatisfied and seven (14%) were dissatisfied or very dissatisfied. The Cochin scale score improved at the second visit (P < 0.0001), with SRM and ES values of 0.66 and 0.58 respectively. The correlation of the change in Cochin score with patient overall satisfaction was r(S) = 0.40. Among the impairment measures, grip strength showed the best responsiveness (SRM = - 0.43, ES = - 0.36, correlation with patient overall satisfaction r(S) = 0.46). The change in Kapandji index had the best correlation (r(S) = 0.51) with patient overall satisfaction but its SRM and ES values were low (- 0.19 and - 0.10 respectively). CONCLUSION: The Cochin scale is responsive and appropriate for the assessment of the effects of surgical treatments on disability in RA hands.     

Calprotectin in patients with rheumatoid arthritis: relation to clinical and laboratory variables of disease activity.

Calprotectin (L1) is a major granulocyte and monocyte protein which is released during activation of these cells. The plasma level of L1 is thought to reflect disease activity in rheumatoid arthritis (RA). In our cross sectional study of 70 patients with RA, L1 had significant correlations with erythrocyte sedimentation rate (r = 0.50), C-reactive protein (r = 0.58), orosomucoid (r = 0.62), platelet count (r = 0.42), leukocyte count (r = 0.33) and IgM rheumatoid factor (r = 0.32); and with the following clinical variables: number of swollen joints (r = 0.24), grip strength (r = -0.22), PIP joint circumferences (r = 0.33) and a combined global assessment score (r = 0.24). L1 was higher in seropositive (median 14,861 micrograms/l) than seronegative patients (median 10,487 micrograms/l) (p less than 0.03).     

Effect of subvalvular disease on results of percutaneous mitral valvotomy]

In order to study the results of percutaneous mitral valvuloplasty (PMV), subvalvular mitral disease was classified using: 1) the transthoracic echo score (0-4), 2) an index derived from left ventricular angiography defined as the ratio of the distance from the extremity of the papillary muscle and the mitral valve in systole and the distance between the beginning of the aortic root and the apex of the left ventricle in diastole. This index of subvalvular fibrosis could be measured in 80 out of our first 103 PMV performed without complication; the mitral surface are a increased from 1.1 +/- 0.4 to 2.2 +/- 0.8 cm2 (p less than 0.0001). After PMV, mitral regurgitation was observed or was aggravated in 28 patients (35%), by one grade in 25 and by more than one grade in 3. The overall echo score was 8.3 +/- 1.5 and that of subvalvular fibrosis was 2 +/- 0.6. The angiographic index of subvalvular fibrosis was 0.18 +/- 0.04. No correlation was observed between echo and angiographic appreciation of subvalvular fibrosis. Multivariate analyses were selected: 1) the overall echocardiographic score (r = -0.45, p less than 0.0001), but not the angiographic index of subvalvular fibrosis or echocardiographic score of subvalvular fibrosis, was predictive of increase of valve surface area; 2) the absence of mitral regurgitation before PMV (p less than 0.01) and an angiographic index of subvalvular fibrosis less than or equal to 0.15 (p less than 0.03) were predictive of increased mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)