Biomedical subjects

V D Steen

Publications and source records attributed to V D Steen.

17 recordsLinked to original sources

PubMed1992

Autoantibody to U3 nucleolar ribonucleoprotein (fibrillarin) in patients with systemic sclerosis.

To determine the clinical significance of serum antibodies to the U3 small nuclear ribonucleoprotein particle ([U3]snRNP), we studied sera from 416 patients with systemic sclerosis (SSc) and 264 controls, using immunofluorescence and immunoprecipitation assays. The presence of serum anti-(U3)snRNP was highly specific to SSc, was found more frequently in blacks, and was associated with skeletal muscle disease and primary pulmonary arterial hypertension. These antibodies may identify one or more unusual clinical subsets of SSc.

Adult↗

PubMed1992

Isolated diffusing capacity reduction in systemic sclerosis.

OBJECTIVE: To determine the long-term outcome of patients with systemic sclerosis (SSc) and an isolated reduction in the diffusing capacity for carbon monoxide (DLCO) at the time of initial evaluation. METHODS: Patients with an isolated reduction in DLCO (i.e., normal forced vital capacity [FVC] and normal ratio of the forced expiratory volume in one second [FEV1] to the FVC) on initial evaluation were identified from among 815 patients with SSc who were carefully followed up throughout their illness. We requested that patients have repeat pulmonary function testing (PFT), and the outcomes of these tests, as well as cardiopulmonary and survival outcomes, were determined. RESULTS: An isolated reduction in DLCO, with a normal FVC was detected in 152 (19%) of the 815 patients. A subset of those with an isolated reduction in DLCO (11%) developed isolated pulmonary hypertension and had severely reduced survival rates. Pulmonary hypertension was strongly associated with an initial DLCO of less than 55% of predicted normal and a FVC (% predicted)/DLCO (% predicted) ratio of greater than 1.4. Among all patients in whom this ratio was greater than 1.4, 22% developed isolated pulmonary hypertension, compared with only 2% of those whose ratio was less than 1.4 (P less than 0.01). Of the 152 patients with isolated DLCO reduction, 73 (48%) underwent PFTs a mean of 5.4 years (range 2.0-13.2) after the initial PFT. Only 6 (8%) of these 73 patients ever had serious pulmonary disease: 5 had isolated pulmonary hypertension, and 1 had severe pulmonary fibrosis. Half of the patients with a low initial DLCO demonstrated a significant improvement (greater than 20%) at followup testing that could not be explained by the demographic, clinical, or laboratory findings at the first visit. CONCLUSION: Isolated reduction in DLCO is a frequent abnormality in SSc. Overall, it is associated with a good prognosis for survival and for pulmonary morbidity. A small subset of patients (11%) who have a very low DLCO (less than 55% of predicted) have developed isolated pulmonary hypertension, all of whom had limited scleroderma.

Carbon Monoxide↗

PubMed1992

Treatment of systemic sclerosis with recombinant interferon-gamma. A phase I/II clinical trial.

OBJECTIVE: A phase I/II trial to examine the safety and efficacy of interferon-gamma (IFN gamma) therapy for patients with systemic sclerosis (SSc). METHODS: An 18-week open-label study was performed. Eighteen patients with rapidly progressive SSc were enrolled, 14 of whom completed at least 16 weeks of the study. These 14 patients had a mean age of 40 years and had been diagnosed as having SSc an average of 10.1 months prior to study entry. Recombinant IFN gamma was injected intramuscularly 3 times weekly for 18 weeks. Six patients received a 0.1 mg/m2 dose, while 8 patients received a 0.5 mg/m2 dose. Patients who completed the 18-week trial were offered maintenance therapy at a dose of up to 0.5 mg/m2. The effects of IFN gamma on skin involvement were assessed by 2 methods: 1) evaluation of skin thickness, by scoring 15 zones according to a 0 (normal skin) to 3 (hidebound skin) scale; and 2) determination of the total body surface area involved, by using 2-dimensional body diagrams to indicate areas affected, and then having a second, "blinded," assessor calculate the area score with a planimeter. RESULTS: The mean skin thickness score decreased from a baseline of 25.9 to 19.1 (P < 0.03), and the mean area scores declined from 33.1 to 19.6 (P < 0.02) after 18 weeks of IFN gamma treatment. Ten patients had a > 25% decrease in area score. Five patients had a > or = 70% decrease in area score, and 3 of them have not experienced disease recurrence for 6 to 17 months after discontinuation of IFN gamma. Five patients withdrew before the study ended. Three of these patients developed renal crisis, which may reflect the severity of the SSc in the study group, although an adverse effect of IFN gamma in SSc cannot be excluded. CONCLUSION: IFN gamma was associated with a beneficial effect on the skin involvement in most of this series of patients with rapidly progressive SSc. A placebo-controlled study will be necessary to confirm these results.

Adult↗

PubMed1992

Comparative studies of esophageal function in systemic sclerosis.

Three modalities for assessing esophageal dysfunction in patients with systemic sclerosis were prospectively compared. Seventeen patients underwent (a) esophageal manometry with measurement of distal esophageal peak contraction pressure amplitude, percentage of peristaltic waves, and lower esophageal sphincter pressure; (b) cine-esophagography with scoring based on residual contrast and the character of visualized waves; and (c) esophageal transit scintigraphy with quantification of residual swallowed tracer. Highly significant correlations were found between scintigraphic residual and cine-esophagography score, between scintigraphic residual and manometric amplitude, and indeed between all pairs of measured esophageal function parameters except those involving lower esophageal sphincter pressure. In addition, scintigraphy and cine-esophagography showed comparable ability to discriminate between patients with abnormal and normal esophageal motor function. Symptoms did not significantly correlate with quantitative parameters, nor did they have diagnostic discriminating ability. Induction of Raynaud's phenomenon in a subgroup of patients had no detectable effect on esophageal function. It was concluded that these three diagnostic modalities are approximately equivalent in their ability to detect esophageal dysmotility in systemic sclerosis and measure its severity.

Adolescent↗

PubMed1992

A monoclonal antibody recognizing Golgi apparatus produced using affinity purified material from a patient with connective tissue disease.

Serum antibodies recognizing the Golgi apparatus have been reported in patients with connective tissue diseases, but little is known of their significance. Serum from a systemic lupus erythematosus patient with polymyositis was found to have high titers of anti-Golgi apparatus antibody. This serum recognized a 64 kD polypeptide in immunoblotting with HEp-2 cells. To verify that the 64 kD polypeptide was associated with the Golgi apparatus and to characterize which Golgi component was recognized, a monoclonal antibody was produced. IgG, isolated from this serum, was used in affinity chromatography to produce purified material which was used to generate a mouse monoclonal antibody. The monoclonal antibody had an indirect immunofluorescent pattern identical to that produced by the patient's serum, and similarly recognized a 64kD polypeptide in immunoblotting. A 59 kD polypeptide was also recognized by the monoclonal antibody, suggesting that the antigens recognized by the monoclonal and serum antibodies may be only partially identical. The antigen appears to be a glycoprotein and an integral component of the Golgi cisternae membranes.

Aged↗

PubMed1991

Early undifferentiated connective tissue disease. I. Early clinical manifestation in a large cohort of patients with undifferentiated connective tissue diseases compared with cohorts of well established connective tissue disease.

We identified a cohort of 410 patients with connective tissue disorders (CTD) of less than or equal to 1 year duration among the participating clinics of the Cooperative Systematic Studies of the Rheumatic Diseases Program. Fifty-seven had rheumatic arthritis (RA), 57 systemic lupus erythematosus, 37 poly/dermatomyositis, 46 scleroderma, and 213 early undifferentiated CTD, including patients with Raynaud's phenomenon, unexplained polyarthritis or at least 3 CTD manifestations such as rashes, myalgias, etc. Baseline clinical data are now being reported. The followup of these patients may prove to be valuable in understanding these diseases. To our knowledge no similar cohort of patients is available for further investigation.

Adolescent↗

PubMed1991

Early undifferentiated connective tissue disease. II. The frequency of circulating antinuclear antibodies in patients with early rheumatic diseases.

The presence of antinuclear antibodies (ANA) in the serum is a common finding in various connective tissue disorders, but usefulness of these antibodies in making diagnoses or prognoses is not known. We report the results of a panel of ANA determinations including ANA, anti-dsDNA, Sm, RNP, SSA, SSB, Jo-1, Scl-70 and PM-1 in 410 patients in a 5-year descriptive study of 410 patients with rheumatic disease symptoms of less than one year's duration. While some patients met diagnostic criteria for a specific rheumatologic diagnosis, others were classified as undifferentiated connective tissue disease (UCTD) and were subclassified by a constellation of symptoms. Our results show that ANA is sensitive in systemic lupus erythematosus (SLE) and progressive systemic sclerosis even in early disease but is not specific. Other "specific" autoantibodies were seen most frequently in SLE but were relatively insensitive and were seen in low frequency in UCTD. ANA have limited diagnostic value in patients with early disease. The prognostic value of these tests will be assessed as the prospective study of these cohorts progresses.

Antibodies, Antinuclear↗

PubMed1990

Outcome of renal crisis in systemic sclerosis: relation to availability of angiotensin converting enzyme (ACE) inhibitors.

OBJECTIVE: To determine the outcome of scleroderma renal crisis before and after the availability of angiotensin converting enzyme (ACE) inhibitors. DESIGN: Evaluation of a large cohort of patients with systemic sclerosis and renal crisis who were followed prospectively. SETTING: University scleroderma center. PATIENTS: One hundred and eight patients who had scleroderma renal crisis between 1972 and 1987. INTERVENTION: ACE inhibitors. MEASUREMENTS AND MAIN RESULTS: Therapy with ACE inhibitors has dramatically improved the survival of patients with scleroderma renal crisis (1-year survival, 15% without and 76% with ACE inhibitors; P less than 0.001). However, 24 (44%) of 55 patients with scleroderma renal crisis who were treated with ACE inhibitors died early or required permanent dialysis. Older age, male sex, an initial serum creatinine level of more than 270 mumol/L, inadequately controlled blood pressure, and congestive heart failure were associated with these poor outcomes, but only older age and congestive heart failure were significant in a multivariate logistic regression analysis. Eleven of twenty patients (55%) who survived dialysis more than 3 months and continued to receive therapy with ACE inhibitors were able to discontinue dialysis after 3 to 15 months compared with 0 of 15 dialysis patients who did not receive ACE-inhibitor therapy (P = 0.002). CONCLUSIONS: Patients with systemic sclerosis who develop hypertension should be treated with an ACE inhibitor. Improved survival and successful discontinuation of dialysis are possible when ACE inhibitors are used to treat scleroderma renal crisis.

Acute Kidney Injury↗

PubMed1990

Pregnancy outcomes in women with primary Raynaud's phenomenon.

Pregnancy outcomes were assessed in 67 women who had well-defined primary Raynaud's phenomenon and in 30 controls, each of whom had been pregnant at least once. Twenty-seven patients had onset of Raynaud's phenomenon prior to any pregnancy, and 37 patients had onset of Raynaud's phenomenon after their last pregnancy. The frequency of miscarriage, stillbirth, and small full-term infants was similar in all 3 study groups. Among the 4 Raynaud's phenomenon patients who had second-trimester miscarriages, 2 of 3 who were tested had moderately positive levels of IgG or IgM anticardiolipin antibody. Premature births were significantly more common in pregnancies that occurred after the onset of Raynaud's phenomenon (24%) than in pregnancies that occurred prior to the onset of Raynaud's phenomenon or in pregnancies among control subjects (9% and 1%, respectively). In addition, the mean weight of the full-term babies of women in both Raynaud's phenomenon groups was significantly less than that of babies born to controls. There were no neonatal deaths or other serious adverse outcomes. These findings may represent yet another manifestation of systemic vasospasm in patients with primary Raynaud's phenomenon.

Abortion, Spontaneous↗

PubMed1990

Systemic sclerosis.

Systemic sclerosis is a disease characterized by several distinctive features. This disease spares children, and its incidence increases steadily with age. Women are affected more than men, especially during childbearing years. Although there is no overall racial predilection, SSc occurs most frequently and severely in young black women. Family and genetic studies suggest only a weak genetic predisposition, but there are many occupational agents that may be implicated in the pathogenesis. The disease with its involvement in many organ systems results in a significant reduction in lifespan. Improvement in survival of renal crisis has been dramatic with the use of ACE inhibitors. Further epidemiologic studies using subsets of patients with more homogeneous clinical and laboratory features will lead to a better understanding of this complex disease.

Humans↗

PubMed1990

Incidence of polymyositis-dermatomyositis: a 20-year study of hospital diagnosed cases in Allegheny County, PA 1963-1982.

The incidence of hospital diagnosed polymyositis-dermatomyositis (PM-DM) among residents of Pittsburgh and Allegheny County, PA was determined from 1963 to 1982. Medical records of all Allegheny County hospitals were searched for patients diagnosed PM-DM, and each accepted case was reviewed and verified by a physician, according to specified criteria. Direct age adjusted incidence rates were computed for race and sex, as new cases/million population/year, with the 1970 Allegheny County population as the standard. One hundred seventy-seven cases were identified during this 20-year survey for a total annual incidence of 5.5/million population. Incidence more than tripled during 1973-1982 compared to the first decade of study, with the greatest increase occurring in black women. Overall, the female to male incidence ratio was 2.2:1, but during the childbearing years (ages 15-44) this ratio increased to greater than 5:1 in both races. Detection of PM-DM is increasing, as shown by temporal trends. Although our series has significantly more adult PM and less DM and overlap cases than other published studies, annual incidence is similar to that reported in other locales.

Age Factors↗

PubMed1990

Epidemiology and natural history of systemic sclerosis.

Systemic sclerosis is an acquired generalized disorder of connective tissue characterized epidemiologically by several distinctive features. From a demographic viewpoint, the disease spares children and its incidence increases steadily with age among adults; is much more frequent in women, especially during the childbearing years; occurs most frequently and severely in young black women, but overall has no prominent racial predilection. If any conclusions can be drawn here, the strongest influences may be age-related hormonal factor and degenerative vascular processes. Family and genetic studies suggest a weak genetic predisposition. There are many environmental agents which may be implicated in pathogenesis. The result of host factors and environmental "triggers" is a multi-system disease which has as prominent features microvascular injury, immunologic dysregulation, and fibroblast activation. The resulting widespread pathologic process leads to vascular insufficiency and fibrosis, which diminishes the reserve function of many organ systems. The result, a significant reduction in lifespan, with a 10-year survival from diagnosis of under 50 per cent. Further epidemiologic studies should take full advantage of established and newly proposed subsets of patients with homogeneous clinical, laboratory, serologic, and natural history features. The environment-host interactions noted above must be fully explored, especially in early untreated disease, where primary rather than secondary mechanisms are most likely to be operative.

Adult↗

PubMed1989

Pregnancy in women with systemic sclerosis.

We assessed fetal morbidity and mortality in women with systemic sclerosis (SSc). Women with a history of SSc and a concomitant pregnancy completed a detailed questionnaire about the pregnancy. These 48 subjects were age-matched and race-matched to 2 other groups of women (a rheumatoid arthritis group and a control group from the same neighborhood), all of whom had been pregnant at least once. There were no differences in the frequencies of miscarriage or perinatal death in the SSc group compared with the 2 control groups. Preterm births occurred slightly more frequently in both SSc patients and rheumatoid arthritis patients compared with the neighborhood control subjects. There were significantly more small full-term infants born to women with SSc. Interestingly, the increase in preterm births and small full-term babies occurred with equal frequency prior to and after the onset of disease. Although close monitoring for premature birth and intrauterine growth retardation is necessary, we conclude that an uneventful, healthy pregnancy is possible for women with SSc. Those with early, rapidly progressive, diffuse skin thickening should avoid becoming pregnant since, intrinsically, they are at higher risk of developing renal crisis.

Abortion, Spontaneous↗

PubMed1989

Normotensive renal failure in systemic sclerosis.

Of 140 patients with "scleroderma renal crisis" encountered during a 33-year period, 15 of 131 (11%) whose blood pressures were recorded were normotensive during this complication. In comparison with 116 patients with hypertension, the normotensive patients significantly more often had microangiopathic hemolytic anemia (90% versus 38%) and thrombocytopenia (83% versus 21%). Pulmonary hemorrhage occurred in 6 normotensive patients. More normotensive patients had received high doses of corticosteroids (prednisone greater than or equal to 30 mg/day) during the 2 months immediately preceding renal crisis (64% versus 16%). A role for corticosteroids in precipitating renal crisis is suggested. The 12-month survival was significantly reduced in the normotensive patients (13% versus 35%).

Acute Kidney Injury↗

PubMed1989

Pulmonary arterial histology and morphometry in systemic sclerosis: a case-control autopsy study.

Morphometric measurements were performed on pulmonary arteries in 58 patients with systemic sclerosis (20 limited cutaneous and 38 diffuse cutaneous involvement [21 with and 17 without renal crisis]) and age, race, and sex matched autopsy controls. Matched pairs analysis was employed. For arteries of all sizes, the area of the intima and percent luminal occlusion were greater in the limited and diffuse (no renal crisis) groups than in controls, and these differences were statistically significant for large and medium sized vessels. The greatest luminal occlusion was found in limited cutaneous patients, and especially those with clinical evidence of pulmonary arterial hypertension, providing a rationale for the poor response to vasodilator therapy in these patients.

Constriction, Pathologic↗

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↗

PubMed1975

Methylmalonicacidemia: biochemical heterogeneity in defects of 5'-deoxyadenosylcobalamin synthesis.

We measured the synthesis of 5'-deoxyadenosylcobalamin (AdoCbl) in fibroblast extracts from patients with inherited methylmalonicacidemia due to deficient activity of the cobalamin-dependent holoenzyme, methylmalonyl-CoA mutase (EC 5.4.99.2). Previous studies with intact fibroblasts from patients whose holoenzyme deficiency was secondary to abnormal cobalamin metabolism had defined two phenotypes, one in which whole cells failed to accumulate AdoCbl and a second in which they failed to accumulate both AdoCbl and the second cobalamin coenzyme, methylcobalamin. With a broken cell assay of AdoCbl synthesis in cell extracts and the cell lines are named cbl A mutants; the other class shows severe deficiency of AdoCbl synthesis and the cell lines are named cbl B mutants. We define cbl C mutants as those in which both AdoCbl and methylcobalamin fail to accumulate in intact cells. The assay for AdoCbl synthesis is thought to measure two enzymatic activities, cob(II)alamin reductase (EC 1.6.99.9) and cob(I)alamin adenosyltransferase (EC 2.5.1.17). Subcellular fractionation studies place this combined activity in mitochondria.

Amino Acid Metabolism, Inborn Errors↗