Myocardial mast cells in systemic sclerosis: a report of three fatal cases.
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Adult↗
Biomedical subjects
J R Seibold
Publications and source records attributed to J R Seibold.
Soluble and cellular markers of immune activation in patients with systemic sclerosis.
The peripheral blood lymphocyte pattern, the lymphocyte responses in vitro, as well as the soluble markers of immune activation were studied in 24 patients with systemic sclerosis (SSc patients). The proportions of total T cells (CD3), their CD4 subset, as well as B lymphocytes were within the normal range. The relative proportion of CD8 lymphocytes, however, was significantly reduced. Patients with SSc had a slightly lower percentage of CD4/4B4+ cells, whereas their proportion of CD4/2H4+ cells was elevated as compared to healthy controls. The proportion of lymphocytes expressing the interleukin-2 receptor (IL-2R) was significantly higher in SSc patients. The proliferative responses of peripheral blood mononuclear cells to PHA stimulation were reduced in the patient group, while expression of IL-2R on lymphocytes after such in vitro stimulation was comparable to that of controls. Expression of IL-2R on patient but not control lymphocytes was increased after in vitro exposure to laminin. Such exposure failed to induce IL-2 production or cell proliferative responses. Soluble plasma IL-2R level (sIL-2R) and soluble CD8 (sCD8) molecule levels in SSc patients were significantly elevated. These results indicate the presence of an ongoing lymphocyte activation in this disease process.
Adult↗
Cyanosis and Raynaud's phenomenon: the relation to underlying disease and venous abnormalities.
Matched groups of 7 to 8 patients with primary Raynaud's phenomenon, systemic sclerosis, and undifferentiated connective tissue disease and cold tolerant normal control subjects were studied by simultaneous digital strain gauge plethysmography and laser Doppler capillary velocimetry during two controlled cycles of hand warming and cooling. Nailfold capillaroscopic assessments and measures of in vivo platelet activation were performed. Triphasic color changes were present in all patients with systemic sclerosis, in 6 of 8 with undifferentiated connective tissue disease, but in only 1 of 7 with primary Raynaud's phenomenon. The occurrence of cyanosis correlated with evidence of impaired venous volume by strain gauge plethysmography and with higher degrees of capillary loop architectural abnormalities. The authors conclude that the presence of digital cyanosis is indicative of connective tissue disease and related to evidence of impaired digital venous capacitance. This may underlie the frequent presence of edema in these patients and may be implicated in the pathogenesis of capillary loop abnormalities.
Adult↗
The effect of local temperature versus sympathetic tone on digital perfusion in Raynaud's phenomenon.
Matched groups of 7 to 8 patients with primary Raynaud's phenomenon, systemic sclerosis, and undifferentiated connective tissue disease and cold-tolerant normal control subjects were studied by simultaneous digital strain gauge plethysmography and laser Doppler capillary velocimetry during two controlled cycles of hand warming and cooling with and without addition of central cooling and during clinical maneuvers to evoke sympathetic tone. Transient vasoconstrictor responses of comparable degree could be evoked in all patient groups and in both the arterial and microvascular beds. While the addition of central cooling had little influence on arterial flow, patients with systemic sclerosis manifested a failure to maintain nutritive perfusion at finger temperatures associated with Raynaud's phenomenon. Linear regression and multivariate analysis suggested that finger temperature was the principal determinant of arterial flow in systemic sclerosis and that arterial flow was the principal determinant of microvascular perfusion. The inability of patients with systemic sclerosis to maintain nutritive flow in the face of either reflex or cold-induced proximal arterial constriction is consistent with their clinical propensity to ischemic tissue injury and separates these patients physiologically from other forms of Raynaud's phenomenon.
Adult↗
Pristane-induced arthritis. The immunologic and genetic features of an experimental murine model of autoimmune disease.
Pristane was injected intraperitoneally into mice of several strains, inducing an inflammatory seropositive arthritis in susceptible strains. The evolving histologic features included synovial hyperplasia, periostitis, and progressive marginal erosions. Multiple serologic immune abnormalities, including rheumatoid factor and anticollagen antibodies, also developed. Genetic analysis indicated that the major histocompatibility complex (H-2), C5 hemolytic complement (Hc), Newcastle disease virus-induced interferon (IF-1), and athymic (nu/nu) loci were involved in regulating susceptibility to pristane-induce arthritis. This experimental murine disease may provide a novel model of rheumatoid arthritis.
Animals↗
Anti-IgE autoantibodies in systemic sclerosis (scleroderma).
An enzyme immunoassay was used to determine the prevalence of anti-IgE auto-antibodies in 66 patients with systemic sclerosis (scleroderma) stratified according to extent and duration of disease. Serum IgG anti-IgE antibodies were detected in 14 (21%) patients and IgM anti-IgE antibodies in nine (14%) patients. The overall prevalence of IgG or IgM isotypes was 21/66, (32%). Anti-IgE autoantibodies were not found in six patients with undifferentiated connective tissue disease or two patients with eosinophilic fasciitis. Attempts to demonstrate histamine release from basophils in vitro by using serum samples containing high titre anti-IgE antibody were unsuccessful. By multivariate analysis the presence of anti-IgE antibody was not associated with duration of systemic sclerosis; extent of scleroderma; specific visceral features, including heart, lung, renal, and gastrointestinal involvement; or mortality.
Autoantibodies↗
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↗
Acute hemodynamic effects of ketanserin in pulmonary hypertension secondary to systemic sclerosis.
A selective antagonist of S2-serotonergic receptors, ketanserin, was administered intravenously during right heart catheterization to 14 patients with pulmonary hypertension complicating systemic sclerosis. A significant reduction in pulmonary vascular resistance was noted which was accompanied by an increase in cardiac output. Paradoxical increase of pulmonary artery pressure occurred in 3 patients, whereas 2 patients with mild pulmonary hypertension normalized both pulmonary pressure and vascular resistance. Our data support the hypothesis that serotonin, released during in vivo platelet activation, influences pulmonary vascular tone in systemic sclerosis.
Adult↗
Paraproteinemia in patients with scleredema. Clinical findings and serum effects on skin fibroblasts in vitro.
Four patients with paraproteinemia and scleredema were studied. Histologic features included marked thickening and fibrosis of the dermis and subcutis. Variable amounts of mucin deposits were detected in the interfibrillar spaces. Serum from one patient significantly stimulated collagen production in normal skin fibroblast cultures, whereas serum from another patient stimulated collagen production in autologous cell cultures. Moreover, serum from one patient stimulated the [35S]sulfate incorporation into the fibroblasts. Circulating serum factors, possibly related to the paraprotein, may enhance the synthesis of extracellular macromolecules by dermal fibroblasts in these patients, thus providing a mechanism for dermal fibrosis.
Aged↗
Anticardiolipin antibodies in systemic sclerosis.
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Adult↗
Cholestasis and fatal agranulocytosis complicating sulfasalazine therapy: case report and review of the literature.
A 55-year-old woman with rheumatoid arthritis in overlap with polymyositis received sulfasalazine for control of synovitis. Cholestatic jaundice, fever, urticaria and agranulocytosis developed after 20 days of treatment and culminated in fatal adult respiratory distress syndrome secondary to Legionella pneumophila. The increasing use of sulfasalazine in the therapy of rheumatoid arthritis mandates that the clinician be aware of this idiosyncratic drug reaction.
Agranulocytosis↗
Selective antagonism of S2-serotonergic receptors relieves but does not prevent cold induced vasoconstriction in primary Raynaud's phenomenon.
In a double blind placebo crossover study, intravenous ketanserin, an antagonist of S2-serotonergic receptors, did not improve plethysmographically monitored digital blood flow during controlled cold challenge in 4 women with carefully defined primary Raynaud's phenomenon. However, ketanserin, if administered at the time of cold induced vasoconstriction, caused prompt vasodilation. These results suggest that serotonin is a contributory element in the maintenance of cold induced vasospasm but that other factors, presumedly adrenergic, initiate the vasoconstrictive response.
Adult↗
Sleep, sleep apnea and the fibromyalgia syndrome.
A patient who presented with primary fibromyalgia syndrome (PFS) was found to have sleep apnea. Since frequent wakening and nonrestorative sleep are prominent clinical complaints in both disorders, we hypothesized an etiologic relationship. A subsequent clinical survey of 11 additional sleep apneics revealed that 3 (27%) fulfilled proposed criteria for PFS. This was significantly greater than local and literature reported studies of nonrheumatologic patients and was comparable to reported prevalence of fibromyalgia in rheumatologic referral populations. A blinded sleep physiology study of 7 patients with PFS revealed a significantly increased percentage of transitional sleep and increased frequency of miniarousals/h, but no significant evidence of occult sleep apnea compared to matched normal controls. The frequent arousals of sleep apnea may be associated with fibromyalgia in some patients but do not explain the sleep disorder of PFS.
Fibromyalgia↗
Influence of the menstrual cycle on Raynaud's phenomenon and on cold tolerance in normal women.
Digital strain gauge plethysmography during a controlled cycle of hand warming and cooling was performed at weekly intervals through a single menstrual cycle in 10 normal women and 6 patients with idiopathic Raynaud's phenomenon (RP). Results were compared to those in 16 additional RP patients and 5 normal males. Maximum digital arterial flow at finger temperature 38 degrees C and reactive hyperemia following three minute arterial occlusion at 30 degrees C was comparable for all groups and did not vary with menstrual status. During cooling, normal women manifested plethysmographic loss of digital arterial flow at finger temperatures (18.1 degrees C +/- 7.9) intermediate between those of normal men (13.7 degrees C +/- 4.3, P less than 0.05) and RP patients (26.0 degrees C +/- 6.1, P less than 0.001). RP patients showed no change in cold tolerance in relation to menstrual status. However, normal women had variable responses to cooling and were found least cold tolerant at the time of menstruation with RP-like responses in all 10 cases although digital color changes were absent. These data support the hypothesis that RP in the premenopausal woman is physiologic and thus, in the majority of cases, not likely to evolve into a definable connective tissue disease.
Adolescent↗
Serotonin and Raynaud's phenomenon.
No single pathophysiologic mechanism explains adequately cold-induced vasospasm in all forms of Raynaud's phenomenon. Local serotonin release from activated platelets is a contributory element in those disorders typified by structural arterial change, e.g., systemic sclerosis (scleroderma). Selective antagonism of S2-serotonergic receptors with ketanserin improves both maximal digital artery flow and cold tolerance. Platelet-derived growth factors, and serotonin itself, may contribute to the fibrotic arteriosclerosis of this disorder. In contrast, in primary (spastic) Raynaud's phenomenon, ketanserin relieves but does not prevent cold-induced vasospasm, which suggests that the role of serotonin is in maintenance of but not provocation of an attack. Antiplatelet therapies could benefit both disorders.
Blood Platelets↗
Plasma beta-thromboglobulin in the differential diagnosis of Raynaud's phenomenon.
Plasma beta-thromboglobulin (beta TG) levels were measured by radioimmunoassay in 61 patients with systemic sclerosis, 19 with carefully defined primary Raynaud's phenomenon, and 8 with Raynaud's phenomenon in suspected transition to systemic sclerosis. Elevated beta TG was present in 50 (82%) patients with systemic sclerosis but levels could not be correlated with duration or extent of disease nor any particular pattern of visceral involvement. Transitional Raynaud's patients had elevated beta TG in 7 (88%) cases, whereas results in patients with primary Raynaud's phenomenon were comparable to normal controls. beta TG, a sensitive measure of in vivo platelet activation, is useful in the differential diagnosis of Raynaud's phenomenon.
Adult↗
Collagen synthesis and collagenase activity in dermal fibroblasts from patients with diabetes and digital sclerosis.
Collagen production and collagenase activity were measured in dermal fibroblast cultures obtained from eight patients with diabetes with digital sclerosis and three normal controls. Total collagen synthesis in patients with diabetes was reduced in comparison with controls. DNA replication was also reduced in patients with diabetes. No differences in collagenase activity were noted. Our results suggest that, in contrast to systemic sclerosis, increased synthesis does not contribute to the collagen accumulation of diabetic digital sclerosis. Decreased degradation related to nonenzymatic glucosylation of collagen is a more likely mechanism.
Adult↗
Family members of crest patients lack serum anticentromere antibody.
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Adolescent↗