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Eugene Y Kissin

Publications and source records attributed to Eugene Y Kissin.

7 recordsLinked to original sources

Durometry for the assessment of skin disease in systemic sclerosis.

OBJECTIVE: To examine the validity of a durometer to objectively measure skin hardness in systemic sclerosis (SSc), and to compare digital durometry with the modified Rodnan skin score (MRSS) and ultrasonography. METHODS: Patients with SSc and healthy controls underwent durometry measurements in 3 assessments: a Latin square experiment to establish durometry's intra- and interobserver reliability compared with skin scoring (5 SSc, 1 control); a longitudinal cohort to assess sensitivity to change in skin hardness (13 SSc, 5 controls); and an ultrasound cohort to evaluate correlation between durometry, ultrasound-measured skin thickness, and clinical skin scoring (30 SSc, 12 controls). RESULTS: Intraobserver reproducibility was higher for durometry than for clinical skin scoring (intraclass correlation coefficient [ICC] 0.97 versus 0.85), whereas interobserver reproducibility was similar (0.75 versus 0.73). Interobserver reproducibility of durometry was good for all body areas (ICC 0.61-0.85), but for skin scoring it was moderate in the legs (0.51) and poor in the abdomen (0.08), feet (0.09), and fingers (0.27). Durometry scores correlated with clinical skin scores (Latin square: r = 0.44, P = 0.03; longitudinal cohort: r = 0.81, P < 0.001) and ultrasound-measured skin thickness (hands: r = 0.58, forearms: r = 0.63, upper arms: r = 0.40; P < or = 0.001 for all). Uninvolved skin in patients with SSc was harder than skin from controls (mean +/- SD 23 +/- 7 durometer units [DU] versus 19 +/- 6 DU; P < 0.0001). Finally, there was a strong correlation between change in MRSS and change in durometry score (r = 0.77, P = 0.002). CONCLUSION: Durometer-measured skin hardness correlates well with MRSS and ultrasound-measured skin thickness, provides greater reliability than MRSS, and is sensitive to changes in skin hardness over time. Durometry should be considered for use in clinical therapeutic SSc trials.

Arm↗

Myofibroblasts and hyalinized collagen as markers of skin disease in systemic sclerosis.

OBJECTIVE: To investigate the correlation between the degree of dermal fibrosis and myofibroblast infiltration using clinical assessments of skin thickness and hardness in systemic sclerosis (SSc). METHODS: Eleven patients with diffuse SSc and 10 healthy controls were evaluated using the modified Rodnan skin thickness score and durometry (hardness measurement). Biopsy samples were obtained from the dorsal mid-forearm in all subjects at the baseline visit and again 6-12 months later in patients with SSc. Five of the patients with SSc received treatment with cyclophosphamide (CYC) in the interval between skin biopsies. Biopsy sections were assessed for myofibroblast and hyalinized collagen content by 2 blinded observers. RESULTS: Myofibroblast and hyalinized collagen scores each correlated with the forearm skin score (r = 0.83, P < 0.0001 and r = 0.78, P < 0.0001, respectively) and with the forearm durometry score (r = 0.72, P < 0.0004 and r = 0.69, P < 0.0008, respectively). The change in the dermal hyalinized collagen score correlated with the change in the forearm durometry score (r = 0.74, P < 0.0213). The myofibroblast score decreased in all 5 patients who received CYC and increased in those receiving non-CYC treatments (P < 0.01 for the difference). CONCLUSION: Myofibroblasts play an important role in the pathogenesis of fibrosis, and our data imply that quantification of myofibroblasts and hyalinized collagen in skin may be a useful outcome measure in clinical studies of SSc.

Adult↗

The effects of intraarticular resiniferatoxin in experimental knee-joint arthritis.

In this study we sought to determine whether an intraarticular administration of a vanilloid agonist resiniferatoxin (RTX) produces an analgesic effect in experimental arthritis. Knee joint inflammation was induced in rats by intraarticular carrageenan (2%, 30 microL). Pain score and left/right hind leg weight distribution ratio were used to assess pain behavior. Changes in knee dimensions were evaluated by measuring external circumference and intraarticular area (ultrasound scanning). The intraarticular administration of RTX (0.0003% or 0.003%, 30 microL) provided a significant analgesic effect. Twenty-four hours after RTX administration, the pain score was reduced from 15.1 +/- 4.7 to 6.9 +/- 4.4 (P < 0.01) with 0.0003% and was abolished (P < 0.0001) with 0.003%. The improvement in weight distribution ratio lasted for several days after the RTX administration. Reduction in knee circumference demonstrated that intraarticular RTX suppressed the carrageenan-induced edema by at least one third. Ultrasound scanning revealed no RTX-induced decrease of the intraarticular area. The experiments demonstrated that intraarticular RTX inhibits pain behavior in knee-joint arthritis and that this effect is dose-dependent. These results suggest a new direction for peripheral analgesia.

Animals↗

Diagnostic imaging in Takayasu arteritis.

PURPOSE OF REVIEW: New imaging modalities may help accurately diagnose and monitor Takayasu arteritis (TAK). Examination of the published literature on arterial imaging studies other than conventional angiography will help guide appropriate use of these studies in TAK. MRI, magnetic resonance angiography (MRA), Doppler ultrasound, CT, and positron emission tomography (PET) are all potentially useful for evaluation of TAK. RECENT FINDINGS: MRI/A avoids the risks of arterial puncture, iodinated contrast load, and radiation exposure, while providing information on arterial wall anatomy and obtaining a generalized arterial survey in TAK. Ultrasound can be helpful in detecting sub-millimeter changes in wall thickness of the carotid arteries and in differentiating TAK from atherosclerotic disease based on minimal plaque content, concentric and long segmental involvement, and location of lesion. Like MRI, CT angiography can be used to detect areas of aortic wall thickening and obtain a generalized survey of the aorta and its proximal branches for areas of stenosis and without the risks associated with arterial puncture. However, CT provides less detailed resolution than ultrasound and incurs the risks of contrast administration. Finally, PET scanning may provide valuable information about cellular activity within an inflamed arterial wall before morphologic changes on other imaging studies. SUMMARY: Although it is still unclear how often early arterial wall changes lead to stenotic lesions, use of these modalities in combination, for both routine monitoring and evaluation of new symptoms, may facilitate the detection of TAK disease activity at a more treatable stage.

Aortography↗

Fibrosis in scleroderma.

The pathogenesis of fibrosis in scleroderma involves a complex set of interactions between the fibroblast and its surroundings. Multiple fibrotic pathways are activated for reasons that are not completely clear, but involve immune activation, microvascular damage, and fibroblast transformation into the myofibroblast. Differential proliferation and apoptosis preserve the myofibroblast phenotype rather that leading to a selective depletion of activated fibroblasts after an acute injury has healed. Disproportionate fibroblast activity could result from a combination of possible cellular and matrix defects that include fibrillin protein abnormalities, autoantibody formation, type II immune response, excessive endothelial reaction to injury, and excessive fibroblast response to TGF-beta. Development of therapies that are targeted to correcting these abnormalities will eventually lead to effective treatment for the fibrotic complications of scleroderma.

Fibroblasts↗

Transforming growth factor beta induces fibroblast fibrillin-1 matrix formation.

OBJECTIVE: Fibrillin, an extracellular matrix protein implicated in dermal fibrosis, is increased in the reticular dermis of systemic sclerosis (SSc) skin. We undertook this study to investigate the hypothesis that transforming growth factor beta (TGFbeta) or other cytokines regulate fibrillin matrix formation by normal and SSc fibroblasts. We further investigated the mechanism of TGFbeta-induced fibrillin fibrillogenesis and its relationship to myofibroblasts. METHODS: Fibrillin and fibronectin matrix deposition and alpha-smooth muscle actin expression by fibroblast cultures from normal and SSc skin treated with TGFbeta or other cytokines were analyzed by immunofluorescence. Supernatant and extracellular matrix from normal and SSc fibroblasts treated with or without TGFbeta were evaluated by Western blot and Northern blot for fibrillin protein and messenger RNA (mRNA) expression, respectively. RESULTS: Immunofluorescence demonstrated increased fibrillin matrix formation by normal and scleroderma fibroblasts after TGFbeta treatment. Other cytokines, including tumor necrosis factor alpha, interleukin-1beta (IL-1beta), IL-4, granulocyte-macrophage colony-stimulating factor, and platelet-derived growth factor, did not affect fibrillin fibrillogenesis. Fibrillin matrix formed in proximity to myofibroblasts and independently of up-regulation of fibronectin matrix or cell number. Western blot analysis of extracellular matrix confirmed increased fibrillin after TGFbeta stimulation of normal or scleroderma fibroblasts. However, TGFbeta did not alter the expression of either soluble fibrillin protein or fibrillin mRNA. CONCLUSION: Our data show that TGFbeta induces fibrillin protein incorporation into the extracellular matrix without affecting fibrillin gene expression or protein synthesis, suggesting that fibrillin matrix assembly is regulated extracellularly. TGFbeta might increase fibrillin matrix by activating myofibroblasts. Such TGFbeta-mediated effects could account for the increased fibrillin matrix observed in SSc skin.

Cells, Cultured↗