Anticytoskeletal autoantibody to microfilament anchorage sites recognizes novel focal contact proteins.

Actin microfilaments are anchored to the plasma membrane at focal contacts. Using an indirect immunofluorescence method, we detected an autoantibody reactive with focal contacts in PtK2, HEp-2, and BHK-21 cells in serum from two patients with early systemic sclerosis. With double immunofluorescence, using the actin-binding drug phalloidin, we localized the plaques decorated by these sera specifically at the termini of microfilament bundles. The reactive antigens were identified by immunoblotting as proteins of 80,000- and 75,300-mol wt in PtK2, and of 53,500-mol wt in HEp-2 and BHK-21 cells. The 53,500-mol wt protein was also identified in rat skeletal, myocardial, and smooth muscle tissues. The detergent solubility of these proteins suggested that they may be linked to the plasma membrane. The autoantigens were immunologically distinct from vinculin and alpha-actinin, two major proteins also known to be concentrated at the ends of microfilament bundles. Our observations suggest that this novel anticytoskeletal autoantibody may identify a novel family of vertebrate cell proteins involved in the linkage of microfilaments to the plasma membrane at focal contacts.

Evaluation of the severity of systemic sclerosis by nailfold capillary microscopy in 112 patients.

The authors used nailfold capillary microscopy (NCM) to evaluate 112 patients with systemic sclerosis spectrum disorders (SSc). Patients were classified as S1 if they had skin involvement proximal to the metacarpo-phalangeal joints. S2 if they had at least two minor SSc American Rheumatism Association criteria, and S3 if they had at least two CREST criteria (calcinosis, Raynaud's, esophageal motility disorder, sclerodactyly, telangiectases), without S1 or S2 criteria. Disease duration from the first symptom was similar in all groups (7.17 +/- 8.98 years). Disease severity was determined by a total score of seven target organ involvements. S1 patients had a greater degree of skin and pulmonary involvement, with a mean score of 26.2 +/- 17.3. S2 patients had a mean score of 13.8 +/- 12.4, and had mostly vascular and digestive involvement, in comparison with S3 patients (7.2 +/- 7.2; p less than 0.001 and p less than 0.01 respectively). NCM sensitivity for S1 and S2 was 93.6%. NCM correlated with the degree of target organ involvement (p less than 0.01). Three NCM profiles established were: "mild," normal or borderline capillaries; "moderate," other abnormalities with no capillary telangiectases; and "severe," abnormalities other than those of the mild profile, with capillary telangiectases.

[Study of peripheral resistance in pregnant women. Preliminary results]. / Etude de la résistance périphérique chez la femme enceinte. Résultats préliminaires.

Variations in blood pressure (BP), heart rate (HR) and peripheral arterial blood flow (BF) were measured during the "roll-over" test (ROV) by impedance plethysmography. With these parameters, the peripheral vascular resistance (PR) was estimated in 17 normotensive and 8 hypertensive women between 28 and 32 weeks of pregnancy. In the normotensive women, a mean drop of 10.97% in BF and mean increase of 49.85% in PR were observed. Chronic hypertensive women with good evolution during pregnancy had a 96.30% (p less than 0.01) drop in their BF and a 399.38% (p less than 0.01) increase in their mean PR. Changes in BF and PR in chronic hypertensive women with obstetrical complications were similar to the normotensive women: BF increased by 4.50% and PR decreased by 0.04%. The increase in PR in the normotensive group could be due to a release of circulating vasopressive agents. In the chronic hypertensive group without complication this release could be more important or there might be an increase in the peripheral vascular sensitivity. In contrast, the lack of variation in PR in the chronic hypertensive group with obstetrical complications could be due to already established arterial vasospasm.

Making people want dentistry.

With millions of dollars being spent by advertisers seeking a share of consumers' disposable income, dentistry is up against fierce competition for patients. Dentistry will have to sell itself to keep up, and one way to do that is to focus on the area in which consumers are increasing their pending-esthetics. Once patients are drawn into a practice by appeals to their desire to look good, they can then be assessed for necessary work to improve their overall dental health.

Making people want dentistry.

With advertisers spending millions of dollars for a share of consumers' disposable income, dentistry is up against fierce competition for patients. Dentistry will have to sell itself to keep up. One way to do this is to focus on the area in which consumers are increasing their spending--esthetics. Patients are drawn to a practice by appeals to their desire to look good. They can then be assessed for necessary work to improve their overall dental health.

Economic burden and cost determinants of deep vein thrombosis during 2 years following diagnosis: a prospective evaluation.

BACKGROUND: Few studies have evaluated the long-term economic consequences of deep vein thrombosis (DVT). None of them have incorporated prospectively collected clinical data to ensure accurate identification of incident cases of DVT and DVT-related health outcomes of interest, such as post-thrombotic syndrome (PTS). OBJECTIVES: To prospectively quantify medical and non-medical resource use and costs related to DVT during 2 years following diagnosis, and to identify clinical determinants of costs. METHODS: Three hundred and fifty-five consecutive patients with acute DVT were recruited at seven Canadian hospital centers. Resource use and cost information were retrieved from three sources: weekly patient-completed cost diaries, nurse-completed case report forms, and the Quebec provincial administrative healthcare database (RAMQ). RESULTS: The rate of DVT-related hospitalization was 3.5 per 100 patient-years (95% confidence interval [CI] 2.2-4.9). Patients reported a mean (standard deviation) of 15.0 (14.5) physician visits and 0.7 (1.2) other healthcare professional visits. The average cost of DVT was $5180 (95% CI $4344-6017) in Canadian dollars, with 51.6% of costs being attributable to non-medical resource use. Multivariate analysis identified four independent predictors of costs: concomitant pulmonary embolism (relative increase in cost [RIC] 3.16; 95% CI 2.18-4.58), unprovoked DVT (RIC 1.65; 95% CI 1.28-2.13), development of PTS during follow-up (RIC 1.35; 95% CI 1.05-1.74), and management of DVT in the inpatient setting (RIC 1.79; 95% CI 1.33-2.40). CONCLUSIONS: The economic burden of DVT is substantial. The use of measures to prevent the occurrence of PTS and favoring outpatient care of DVT has the potential to diminish costs.

Relation between D-dimer level, venous valvular reflux and the development of post-thrombotic syndrome after deep vein thrombosis.

BACKGROUND: The pathophysiology of post-thrombotic syndrome (PTS) is postulated to involve persistent venous obstruction and venous valvular reflux. OBJECTIVE: To study the association between D-dimer level, valvular reflux and the PTS in a well-defined cohort of deep vein thrombosis (DVT) patients. METHODS: Consecutive patients with acute symptomatic DVT were recruited at eight centers and were followed for 24months. D-dimer was measured at 4months. A standardized ultrasound assessment for popliteal valvular reflux was performed at 12months. Using the Villalta scale, patients were assessed for PTS during follow-up by evaluators who were unaware of D-dimer or reflux results. RESULTS: Three hundred and eighty-seven patients were recruited; of these, 305 provided blood samples for D-dimer and 233 had a 12-month reflux assessment. PTS developed in 45.1% of subjects. Mean D-dimer was significantly higher in patients with vs. without PTS (712.0 vs. 444.0µgL(-1) ; P=0.02). In logistic regression analyses adjusted for warfarin use at the time of D-dimer determination and risk factors for PTS, D-dimer level significantly predicted PTS (P=0.03); when stratifying for warfarin use at the time of blood draw, adjusted odds ratio (OR) for developing PTS per unit difference in log D-dimer was 2.33 (95% CI 0.89, 6.10) in those not on warfarin vs. 1.25 (95% CI 0.87, 1.79) in those on warfarin. Ipsilateral reflux was more frequent in patients with moderate-to-severe PTS than in patients with mild PTS (65% vs. 40%, respectively; P=0.01) and was independently associated with moderate-to-severe PTS in logistic regression analyses (P=0.01). CONCLUSION: D-dimer levels, measured 4months after DVT in patients not on warfarin, are associated with subsequent development of PTS. Venous valvular reflux is associated with moderate-to-severe PTS.

Determinants of health-related quality of life during the 2 years following deep vein thrombosis.

BACKGROUND/OBJECTIVES: We prospectively measured change in quality of life (QOL) during the 2 years after a diagnosis of deep vein thrombosis (DVT) and evaluated determinants of QOL, including development of the post-thrombotic syndrome (PTS). PATIENTS/METHODS: Consecutive patients with acute DVT were recruited from 2001 to 2004 at eight hospitals in Canada. At study visits at baseline, and 1, 4, 8, 12 and 24 months, clinical data were collected, standardized PTS assessments were performed, and QOL questionnaires were self-completed. Generic QOL was measured using the Short-Form Health Survey-36 (SF-36) questionnaire. Venous disease-specific QOL was measured using the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Sym questionnaire. The change in QOL scores over a 2-year follow-up was assessed. The influence of PTS and other characteristics on QOL at 2 years was evaluated using multivariable regression analyses. RESULTS: Among the 387 patients recruited, the average age was 56 years, two-thirds were outpatients, and 60% had proximal DVT. The cumulative incidence of PTS was 47%. On average, QOL scores improved during follow-up. However, patients who developed PTS had lower scores at all visits and significantly less improvement in QOL over time (P-values for PTS*time interaction were 0.001, 0.012, 0.014 and 0.006 for PCS, MCS, VEINES-QOL and VEINES-Sym). Multivariable regression analyses showed that PTS (P < 0.0001), age (P = 0.0009), proximal DVT (P = 0.01) and inpatient status (P = 0.04) independently predicted 2-year SF-36 PCS scores. PTS alone independently predicted 2-year VEINES-QOL (P < 0.0001) and VEINES-Sym (P < 0.0001) scores. CONCLUSIONS: Development of PTS is the principal determinant of health-related QOL 2 years after DVT. Our study provides prognostic information on patient-reported outcomes after DVT and emphasizes the need for effective prevention and treatment of the PTS.

[Peripheral vascular effects of metoprolol, pindolol and propranolol in hypertensive patients]. / Effets vasculaires périphériques du métoprolol, pindolol et propranolol chez des patients hypertendus.

Hemodynamic parameters, after administration of three different beta-blockers, were measured in fifteen hypertensive, and five normotensive, subjects. The non-invasive hemodynamic measurements were made prior to drug administration, after the first dose, and after prolonged treatment with either: metoprolol (M) 100 mg b.i.d., propranolol (Pr) 80 mg b.i.d., or pindolol (P) 10 mg b.i.d. With the parameters of blood pressure (B.P.), pulse rate (H.R.), blood flow in the leg at rest were determined with the plethysmographic impedance technique; venous compliance (V.C.), and flow in the leg after reactional hyperemia (F.R.H.) were evaluated by the mercury gauge technique. The pneumoplethysmographic technique was used to measure digital flow (D.F.). During administration of metoprolol, the B.P. and H.R. decreased significantly in the first few hours, and remained so during the prolonged treatment period of 4 weeks; the other parameters did not change significantly. Propranolol, after short-term treatment, decreased H.R. and blood flow in the leg at rest. Also, modifications in the venous compliance occurred but are difficult to interpret. After administration of pindolol, except for a decrease in H.R. and reactional hyperemia that occurred during the 2nd hour, no significant changes occurred in the other parameters. The digital flow showed non-significant variations. These preliminary results demonstrate that the changes registered through non-invasive techniques, although very small, affect pindolol less than metoprolol or propranolol.

The role of intravenous streptokinase in acute arterial occlusions after cardiac catheterization.

Arterial occlusions after cardiac catheterization are usually treated surgically. We report four patients with femoral thrombosis or distal emboli that developed after cardiac catheterization. Each patient was treated successfully with intravenous streptokinase. Therapy was initiated 1-60 hr after the procedure. The duration of infusion lasted 4-42 hr (mean 27 hr). Pulses were restored 4-19 hr (mean 10 hr) after the beginning of infusion. There was no major hemorrhagic complication, even in patients with very early streptokinase infusion. Thus intravenous streptokinase may be an alternate choice to surgery for arterial occlusions after invasive procedures.

Anticentromere autoantibodies. Evaluation of an ELISA using recombinant fusion protein CENP-B as antigen.

OBJECTIVE: To evaluate an enzyme-linked immunosorbent assay (ELISA) for anticentromere autoantibodies (ACA). METHODS: Sera from 611 patients with scleroderma, CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), Raynaud's disease, and connective tissue disease control patients were studied by ELISA using the fusion protein CENP-B, by immunofluorescence on dividing HEp-2 cells, and by immunoblotting on chromosomes and CENP-B. RESULTS: Compared with immunofluorescence, the CENP-B ELISA sensitivity was 94% and the specificity was 93%. In 19.7% of the cases, there was a probability of a false-positive result and in 1.9%, a probability of a false-negative result, yielding positive and negative predictive values of 0.80 and 0.98, respectively. CONCLUSION: The CENP-B ELISA is a sensitive and specific assay for ACA.

Prognostic significance of anticentromere antibodies and anti-topoisomerase I antibodies in Raynaud's disease. A prospective study.

Seventy-seven patients with Raynaud's disease were studied for a mean of 4 years (range 1-11 years) to determine the relationship between autoantibodies and long-term clinical outcome. Anticentromere antibodies (ACA) were assayed by indirect immunofluorescence and by immunoblotting of HeLa cell chromosome extracts. Antibodies to topoisomerase I (anti-topo I) were assayed by immunodiffusion and immunoblotting. Antibodies to the major centromeric protein, CENP-B, and anti-topo I were studied by enzyme-linked immunosorbent assay (ELISA). Eight patients developed telangiectasias, 4 developed skin tightening, and 4 developed a connective tissue disease other than scleroderma. The presence of ACA at the start of the study was associated with the development of telangiectasias (P less than 0.003). An initial 100-kd band on immunoblot in conjunction with a positive anti-topo I ELISA result was associated with the development of tight skin (P less than 0.0025), while a 100-kd band with a negative anti-topo I ELISA result was associated with the subsequent development of a connective tissue disease other than scleroderma (P less than 0.0073). Patients who were initially ACA positive, had the 100-kd band on immunoblot, or had positive ELISA results for anti-topo I or for anti-CENP-B were 63-fold more likely to develop signs of connective tissue disease by the end of the study (P less than 0.000009). The presence of any of these autoantibodies was more sensitive (100%), although less specific (75%), than were findings from nailfold capillaroscopy (sensitivity 67% and specificity 95%) in predicting subsequent clinical progression. We conclude that findings of assays for anti-topo I and ACA complement the findings from nailfold capillaroscopy in providing useful prognostic information in Raynaud's disease.