Biomedical subjects

V D Steen

Publications and source records attributed to V D Steen.

At least 73 records · Page 4Linked to original sources

PubMed1988

Correlates between autoantibodies to nucleolar antigens and clinical features in patients with systemic sclerosis (scleroderma).

Immunofluorescence on rat liver sections was used to select high-titer antinucleolar antibodies (ANoA) in the sera of patients with systemic sclerosis (scleroderma). In 646 patients, 53 ANoA sera (8%) were identified, and of these, 46 were available in sufficient quantities for further analysis. The complex of RNA polymerase I was immunoprecipitated by 7 sera (15%), which uniformly produced punctate nucleolar staining. The PM-Scl antigen, a particle consisting of 11 polypeptides, was immunoprecipitated by 8 sera (17%), all of which displayed homogeneous nucleolar staining. A 34-kd nucleolar protein (fibrillarin) of the U3 RNP complex was positive in immunoblotting of 22 sera (48%), which characteristically produced clumpy nucleolar staining. Antibodies against RNA polymerase I were associated with diffuse scleroderma of short duration, which was characterized by a high prevalence of internal organ involvement, including renal crisis. Anti-U3 RNP antibodies had a high prevalence in men with significantly less joint involvement, compared with ANoA-negative patients. Anti-PM-Scl antibodies identified a group of scleroderma patients with a high prevalence of concomitant myositis and renal involvement.

Antibodies, Antinuclear↗

PubMed1988

Phenothiazine-induced systemic lupus erythematosus with superior vena cava syndrome: case report and review of the literature.

Phenothiazine-induced lupus with circulating anticoagulant (CAC) has been reported infrequently, and is rarely associated with significant symptoms. We describe a patient who we suspect had perphenazine-induced lupus erythematosus with CAC. She had recurrent episodes of venous thrombosis and ultimately developed superior vena cava syndrome. The relationships among phenothiazine-induced lupus, CAC, and thrombosis are discussed.

Adult↗

PubMed1988

Reduced natural killer cell activity in patients with systemic sclerosis. Correlation with clinical disease type.

Natural killer (NK) cell number and function were determined in 69 systemic sclerosis (SSc) patients (41 with diffuse cutaneous SSc, 24 with limited cutaneous SSc, and 4 with scleroderma in an overlap syndrome). The results were compared with those obtained from 5 patients with Raynaud's disease and from 27 normal controls. Natural and antibody-dependent killing was reduced in the total group of SSc patients compared with controls, but these differences were primarily attributable to patients with the diffuse form of the disease who were seen early in their illness (less than 5 years after onset). NK cell numbers were not significantly reduced in patients compared with controls, although lower numbers were observed in individuals with early diffuse disease. Other clinical parameters, such as treatment with D-penicillamine or the presence of scleroderma-specific autoantibodies, did not exert an independent effect on NK cell function. These findings suggest a possible central role for NK cells in the pathogenesis of SSc.

Adult↗

PubMed1988

Prognostic importance of cardiac arrhythmias in systemic sclerosis.

Ambulatory electrocardiography was performed in 183 patients with systemic sclerosis recruited from five centers who were selected to reflect a balanced population with respect to disease extent and duration. Ventricular ectopy occurred in 67 percent of patients and was strongly correlated by both univariate and multivariate analyses with total mortality and with sudden death. By multivariate analysis, ventricular ectopy was strongly associated with increasing patient age and with other evidence of cardiac and pulmonary involvement but not with clinical and laboratory measures of duration and extent of systemic sclerosis. Evidence of myocardial fibrosis thought to be secondary to microvascular alteration is common in systemic sclerosis, but the clinical implications of myocardial involvement are less well appreciated. The present data suggest the need for ambulatory electrocardiography in the clinical assessment of selected patients with systemic sclerosis, especially those with cardiac or pulmonary involvement, as well as for studies of the effects of antiarrhythmic therapy.

Adolescent↗

PubMed1988

Cutaneous hypoxia in patients with systemic sclerosis (scleroderma).

Measurement of transcutaneous oxygen pressure (TCPO2) is an established and noninvasive way of assessing cutaneous hypoxia. Since the degree of oxygenation modulates fibroblast growth and synthesis, we investigated the presence of cutaneous hypoxia in patients with systemic sclerosis (SS). We measured TCPO2 of the involved skin of the dorsal aspect of the forearm in 33 patients with SS and 16 control individuals (normal subjects and patients with Raynaud's disease). The degree of forearm skin thickness was assessed clinically as mild, moderate, or severe. The TCPO2 measurements were obtained at a sensor temperature of 44 degrees C, which causes maximal vasodilation and eliminates the variables associated with vascular tone. Measurements were recorded while patients were breathing room air or 31% oxygen delivered by a Ventimask system (Baxter Healthcare, Ocala, Fla). We also measured the TCPO2 of the medial aspect of the arm when this site was uninvolved. We found that sclerodermatous skin is hypoxic when compared with the uninvolved skin of patients with SS or control individuals. The TCPO2 values were indirectly related to skin thickness; thus, patients whose skin was severely thickened had the lowest TCPO2 values. There was no correlation of TCPO2 values with pulmonary function tests or arterial oxygen pressure. The TCPO2 levels of patients with Raynaud's disease did not differ from other control individuals. The administration of oxygen increased TCPO2 readings in patients with SS to normal values. We conclude that the thickened skin of patients with SS is hypoxic and suggest that TCPO2 measurements may be helpful in objectively assessing the degree of skin thickness. The hypoxia demonstrated in SS skin may play a role in the modulation of dermal fibroblast proliferation and synthetic activity.

Adult↗

PubMed1987

Surgery for scleroderma of the hand.

The role of hand surgery in systemic sclerosis (scleroderma) has been documented infrequently. Out of a series of 813 consecutive patients with scleroderma, 31 have had one or more surgical procedures on their involved hands--a total of 52 operations. Raynaud's phenomenon and digital tip ulcerations have been controlled medically by vasodilators and meticulous local wound care. Most digital ulcerations progressing to frank gangrene have been allowed to autoamputate to maximize the length of the salvaged finger, but 23 digital amputations have been performed when conservative measures failed. Digital sympathectomy and microsurgical revascularization have produced relief of symptoms in several patients. Severe flexion contractures of the proximal interphalangeal (PIP) joints, with secondary hyperextension of the metacarpophalangeal (MP) joints, have been effectively treated by arthrodesis of the PIP joints in 44 to 55 degrees of flexion. This has allowed both improved hand function and primary healing of dorsal ulcers in 53 PIP joints in 12 patients.

Adolescent↗

PubMed1987

Vasculitis in systemic sclerosis: association with Sjögren's syndrome and the CREST syndrome variant.

We describe 7 patients with established systemic sclerosis who developed clinical evidence of vasculitis 1 to 33 (mean 12.7) years after the first symptoms of scleroderma. Six had the CREST variant of systemic sclerosis and also had features of Sjögren's syndrome (SS). Five of 6 patients tested had serum anti-SSA (Ro) antibodies. Vasculitis presented primarily as cutaneous lesions with ulceration and/or mononeuritis multiplex, and 6 patients had severe systemic manifestations. Vasculitis was histopathologically documented in 6 cases in biopsies of skin (4 of 4), muscle (2 of 3) and sural nerve (3 of 3). Patients with systemic sclerosis with CREST syndrome and SS appear to be at increased risk to develop vasculitis.

Aged↗

PubMed1986

Pulmonary hypertension in the CREST syndrome variant of systemic sclerosis.

Pulmonary hypertension (PHT) occurred in 59 (9%) of 673 systemic sclerosis patients seen between 1963 and 1983. In 30 patients, all with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), the pulmonary hypertension was isolated, i.e., independent of other pulmonary or cardiac conditions. In 20 patients, isolated PHT was demonstrated by cardiac catheterization. All had normal or only mildly decreased lung volumes, and mild or no pulmonary interstitial fibrosis on chest roentgenogram. In comparison with 287 CREST syndrome patients without PHT, these 20 patients had markedly reduced diffusing capacity for carbon monoxide (DLCO) (mean 39% of predicted normal). In 6 patients, the low DLCO antedated clinical evidence of PHT by 1-6 years. At autopsy there was marked intimal fibrosis with hyalinization and smooth muscle hypertrophy in the small- and medium-sized arteries, without significant parenchymal fibrosis or inflammation. Patients with isolated PHT did not respond favorably to vasodilators and had a very poor prognosis, with a 2-year cumulative survival rate of 40%. A DLCO less than 45% of predicted in the absence of pulmonary interstitial fibrosis may be an important predictor of the subsequent development of isolated PHT.

Calcinosis↗

PubMed1986

Anti-SS-A antibodies and fetal outcome in maternal systemic lupus erythematosus.

In 155 women with systemic lupus erythematosus, there were no significant differences in the rates of fertility or adverse fetal outcome between the 47 (30%) with serum anti-SS-A antibody and the 108 without anti-SS-A, except in the frequency of congenital heart block. This complication occurred in 6 of 96 pregnancies in women with anti-SS-A and was associated with high-titer maternal antibody. The overall risk of a woman with lupus having an infant with congenital heart block was estimated to be 1:60, but the risk was considerably higher (1:20) if anti-SS-A antibody was present.

Abortion, Spontaneous↗

PubMed1986

The toxicity of D-penicillamine in systemic sclerosis.

We studied D-penicillamine toxicity in 259 patients with systemic sclerosis treated since 1972. The average daily dose of 635 mg was given for a mean of 1.8 years. Of patients with systemic sclerosis, 47% has side effects from D-penicillamine treatment, similar to the 56% of 807 patients with rheumatoid arthritis in seven separate series. Individual manifestations of toxicity included rash, proteinuria, gastrointestinal symptoms, dysgeusia, oral ulcers, thrombocytopenia, and neutropenia. Four episodes each of myasthenia gravis and pemphigus occurred in our patients; both were reported rarely in patients with rheumatoid arthritis. Adverse effects occurred more frequently after rapid increases in dosage. Treatment had to be discontinued due to toxicity in 29% of patients with systemic sclerosis and in 33% of those with rheumatoid arthritis. Although toxic, with a high frequency of adverse effects, D-penicillamine can be used safely in the treatment of systemic sclerosis. Pemphigus and myasthenia gravis may occur more frequently with therapy for systemic sclerosis than with that for rheumatoid arthritis.

Arthritis, Rheumatoid↗

PubMed1985

Evolution of primary Raynaud's phenomenon (Raynaud's disease) to connective tissue disease.

Eighty-seven patients diagnosed as having primary Raynaud's phenomenon (Raynaud's disease) were reexamined after this symptom had been present for a mean of 8.8 years (range 2.0-34.5). One or more additional clinical feature(s) suggesting an underlying connective tissue disease were found in 12 patients (14%) at first evaluation, and in 23 (26%) by the last evaluation. The most frequent findings were puffy fingers (10 patients), digital tip pitting scars (8 patients), and digital tip ulcerations (6 patients). Distal esophageal hypomotility and/or decreased pulmonary diffusing capacity for carbon monoxide were found in 12 patients. Only 4 individuals (5%) developed clear evidence of a connective tissue disease, and in all cases, the diagnosis was the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) syndrome variant of systemic sclerosis. This condition became obvious 8-17 years after the onset of Raynaud's phenomenon. One or more serologic test values were initially abnormal in 2 of these CREST syndrome patients, as well as in 12 patients who continued to have primary Raynaud's phenomenon at the last evaluation. The combination of puffy fingers, digital pitting scars, and serum anticentromere antibody, all consistent with CREST syndrome, occurred in a small group of patients. None of the 78 patients whose serologic tests were repeated during followup had a change in the serologic profile. These results suggest that only a small proportion of patients with primary Raynaud's phenomenon develop one of the connective tissue diseases during the first decade after onset. When such a disorder does appear, systemic sclerosis with the CREST syndrome variant is the most likely eventual diagnosis.

Adolescent↗

PubMed1985

Double-blind, multicenter controlled trial comparing topical dimethyl sulfoxide and normal saline for treatment of hand ulcers in patients with systemic sclerosis.

A prospective, randomized, double-blind trial compared topical therapy with 0.85% normal saline, 2% dimethyl sulfoxide (DMSO), and 70% DMSO for treatment of digital ulcers in 84 patients with systemic sclerosis. There were no statistically significant differences among the 3 treatment groups in the improvement in the total number of open ulcers, total surface area of open ulcers, average surface area per open ulcer, number of infected ulcers, number of inflamed ulcers, or patient pain assessment. While some patients improved during the study, improvement could not be attributed to a specific treatment. Over one-quarter of the patients treated with 70% DMSO were withdrawn for significant skin toxicity.

Administration, Topical↗

PubMed1985

Pulmonary involvement in systemic sclerosis (scleroderma).

One hundred sixty-five nonsmoking systemic sclerosis patients were evaluated by pulmonary function testing. Restrictive lung disease and an isolated reduction of the diffusing capacity of carbon monoxide were the most frequent abnormalities. Patients with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) had a similar frequency and severity of pulmonary involvement compared with the patients who had diffuse scleroderma. CREST syndrome patients with restrictive lung disease rarely had the anticentromere antibody and had more skin and joint involvement of their hands, compared with other CREST syndrome patients. Dyspnea and rales were most commonly found in patients with restrictive lung disease. Fibrosis, shown on chest radiograph, and pulmonary function abnormalities correlated poorly with each other. Dyspnea was associated with restrictive disease, and rales were more commonly found in patients with fibrosis. Patients with a restrictive abnormality had the worst prognosis, with a 5-year survival rate of 58%, although death from pulmonary causes was uncommon. Comparison of these nonsmoking patients with 137 scleroderma patients who smoked, seen during the same time period, revealed more frequent and severe obstructive changes in smokers. Smoking patients with restrictive lung disease had more severe disease than nonsmoking patients. The single breath diffusing capacity for carbon monoxide was significantly decreased in the patients who smoked compared with the nonsmokers. These data confirm that pulmonary function abnormalities are common in patients with systemic sclerosis including CREST syndrome. Smoking appears to have an additive deleterious effect on pulmonary function and should be strongly discouraged.

Calcinosis↗

PubMed1985

The effect of D-penicillamine on pulmonary findings in systemic sclerosis.

D-penicillamine has been used for the treatment of systemic sclerosis for 2 decades. Forty-four systemic sclerosis patients who received a mean dose of 636 mg of D-penicillamine for 2.3 years and 48 untreated patients, who had repeat pulmonary function tests performed after a mean of 3.5 and 4.8 years, respectively, were evaluated. There were no significant changes in the vital capacity or the forced expiratory volumes during this time in either group. However, the diffusing capacity for carbon monoxide improved from 76% of predicted to 87% of predicted in D-penicillamine-treated patients. Untreated patients changed slightly, from 73% of predicted to 76% of predicted. When multiple logistic regression analysis was used to account for factors which could have biased treatment comparisons, the improvement related to use of the D-penicillamine was significant (P less than 0.05). This improvement in the D-penicillamine-treated patients was associated with no further progression of dyspnea or fibrosis on chest radiograph, as well as reduced skin thickening. These data suggest that D-penicillamine may be useful in the treatment of systemic sclerosis that involves the lung; however, further studies are needed.

Colchicine↗

PubMed1985

The electrocardiogram in systemic sclerosis (scleroderma). Study of 102 consecutive cases with functional correlations and review of the literature.

The electrocardiographic findings in 102 consecutive patients with scleroderma were reviewed to determine the frequency and nature of the electrocardiographic abnormalities associated with this disease. Septal infarction pattern unassociated with QRS prolongation was present in 10 percent, compared with none of 96 control subjects (p less than 0.001). Ventricular conduction abnormalities were present in 17 percent. A normal electrocardiogram was obtained in 49 percent. A subset of 48 patients underwent detailed cardiopulmonary evaluation including exercise thallium scintigraphy, rest and exercise radionuclide ventriculography, pulmonary function tests, and chest roentgenography. Functional correlations of the electrocardiographic findings were examined in this subset. Septal infarction pattern (five of 48) and ventricular conduction abnormalities (10 of 48) were both associated with septal or anteroseptal thallium perfusion abnormalities (10 of 15 versus six of 33 of the remainder, p less than 0.005), which were present despite normal coronary angiographic results. Thallium defect scores were greater in patients with septal infarction pattern or ventricular conduction abnormalities compared with the remainder (defect scores 3.0 +/- 2.6 versus 1.4 +/- 2.2, respectively, p less than 0.025). In patients with ventricular conduction abnormalities, both left bundle branch block and right bundle branch block with left anterior fascicular block were associated with abnormal left ventricular function, whereas isolated right bundle branch block or left anterior fascicular block was associated with normal left ventricular function. A normal electrocardiographic finding (19 of 48) was associated with normal left ventricular function at rest (19 of 19). However, 11 of 19 (58 percent) had thallium perfusion defects and four of 19 (21 percent) had an abnormal response to exercise, although in none was the peak ejection fraction less than 50 percent. It is concluded that both septal infarction pattern and ventricular conduction abnormalities are electrocardiographic abnormalities associated with scleroderma heart disease; they appear to be a result of myocardial fibrosis. Some degree of myocardial fibrosis may be present with a normal electrocardiographic result, but significant left ventricular dysfunction is unlikely. Septal infarction pattern and ventricular conduction abnormalities, when present, are indicators of more advanced fibrosis.

Adult↗

PubMed1984

Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma.

To investigate cardiopulmonary function in progressive systemic sclerosis with diffuse scleroderma, we studied 26 patients with maximal exercise and redistribution thallium scans, rest and exercise radionuclide ventriculography, pulmonary-function testing, and chest roentgenography. Although only 6 patients had clinical evidence of cardiac involvement, 20 had abnormal thallium scans, including 10 with reversible exercise-induced defects and 18 with fixed defects (8 had both). Seven of the 10 patients who had exercise-induced defects and underwent cardiac catheterization had normal coronary angiograms. Mean resting left ventricular ejection fraction and mean resting right ventricular ejection fraction were lower in patients with post-exercise left ventricular thallium defect scores above the median (59 +/- 13 per cent vs. 69 +/- 6 per cent [P less than 0.025], and 36 +/- 12 per cent vs. 47 +/- 7 per cent [P less than 0.025], respectively). We conclude that in progressive systemic sclerosis with diffuse scleroderma, abnormalities of myocardial perfusion are common and appear to be due to a disturbance of the myocardial microcirculation. Both right and left ventricular dysfunction appear to be related to this circulatory disturbance, suggesting ischemically mediated injury.

Adult↗

PubMed1984

Clinical and laboratory associations of anticentromere antibody in patients with progressive systemic sclerosis.

Anticentromere antibody (ACA) was found in the serum of 4 (3%) of 120 patients with progressive systemic sclerosis with diffuse scleroderma and in 69 (49%) of 141 with progressive systemic sclerosis with the CREST syndrome variant. The 69 CREST syndrome patients with ACA were compared with the 72 CREST syndrome patients without ACA. The former were older at the onset of symptoms and significantly more frequently female (97% versus 78%, P less than 0.01). Those with ACA more often had telangiectasiae of the digits (93% versus 75%) and calcinosis (55% versus 22%). These differences were also present after the groups were stratified according to duration of disease. Cutaneous involvement was similar in both degree and extent in the 2 groups; 20% of CREST patients both with and without ACA had forearm skin thickening. Pulmonary interstitial fibrosis on chest roentgenogram and restrictive disease on pulmonary function testing were significantly less frequent in the ACA patients. Gastrointestinal involvement, pulmonary arterial hypertension, and cardiac abnormalities were similar in both groups, and there has been no difference in survival between CREST syndrome patients with and without ACA. Tissue typing studies revealed a significant association between ACA and HLA-DR1.

Adult↗

PubMed1984

Myocardial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis. Exercise radionuclide evaluation and comparison with diffuse scleroderma.

Myocardial function and perfusion were evaluated in 22 patients with progressive systemic sclerosis with the CREST syndrome using exercise and radionuclide techniques, pulmonary function testing, and chest roentgenography. The results were compared with a similar study of 26 patients with progressive systemic sclerosis with diffuse scleroderma. The prevalence of thallium perfusion abnormalities was similar in the groups with CREST syndrome and diffuse scleroderma, (64 percent versus 77 percent), but the defects were significantly smaller in the CREST syndrome (p less than 0.01). Reperfusion thallium defects in the absence of extramural coronary artery disease were seen in 38 percent of patients with diffuse scleroderma. This finding was not seen in any of the patients with the CREST syndrome. In diffuse scleroderma, abnormalities of both right and left ventricular function were related to larger thallium perfusion defects. In the CREST syndrome, abnormalities of left ventricular function were minor, were seen only during exercise, and were unrelated to thallium perfusion defects. Abnormal resting right ventricular function was seen in 36 percent of the patients with the CREST syndrome and was associated with an isolated decrease in diffusing capacity of carbon monoxide. It is concluded that the cardiac manifestations of the CREST syndrome are distinct from those found in diffuse scleroderma. Unlike diffuse scleroderma, abnormalities of left ventricular function in the CREST syndrome are minor and are unrelated to abnormalities of coronary perfusion. Right ventricular dysfunction in the CREST syndrome appears to be primarily related to pulmonary vascular disease.

Adult↗