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Shawn E Cowper

Publications and source records attributed to Shawn E Cowper.

16 recordsLinked to original sources
PubMed2006

Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a disease of unknown etiology that affects a subset of patients with renal insufficiency. Recent publications suggested an association between exposure to gadolinium-containing contrast agents and subsequent development of NSF. We sought to detect gadolinium within the skin and soft tissue of patients with NSF who were exposed to gadolinium-based contrast. METHODS: Paraffin-embedded skin and soft tissue from NSF patients exposed to gadolinium, and from negative controls, was provided by the NSF Registry (New Haven, Conn). The tissue was searched for metals using a field emission scanning electron microscope that was equipped with energy dispersive spectroscopy. The presence of gadolinium and other metals was verified through identification of unique and requisite X-ray emission spectra. RESULTS: Gadolinium was detected in 4 of 13 tissue specimens from 7 patients with documented NSF who were exposed to gadolinium-based radiographic contrast. No gadolinium was detected in a paraffin-embedded specimen from a negative control. Based upon the known exposure history of patients with detectable gadolinium, a tissue residence time of 4 to 11 months was observed. LIMITATIONS: As this was a pilot investigation, only a single control specimen and a single histological section from each block of tissue were utilized. CONCLUSION: In this pilot investigation, gadolinium was detected in the tissue of a number of patients with NSF. Although neither dispositive of a pathophysiologic mechanism, nor proof of causation, the detection of gadolinium within tissue of NSF patients is supportive of an epidemiologic association between exposure to gadolinium-containing contrast material and development of disease.

Acidosis↗
PubMed2006

The role of circulating fibrocytes in fibrosis.

Fibrocytes are cells that circulate in the peripheral blood and produce connective tissue proteins such as vimentin and collagens I and III. Fibrocytes are associated with skin lesions, pulmonary fibrosis, and tumors and they contribute to the remodeling response by secreting matrix metalloproteinases. Fibrocytes can further differentiate, and they are a likely source of the contractile myofibroblast that appears in many fibrotic lesions. There is evidence in the skin for a prominent role for fibrocytes in the development of hypertrophic scars and keloids. In asthma or in experimental models of pulmonary fibrosis, fibrocytes have been shown to infiltrate areas of inflammation and tissue damage. Fibrocytes constitute part of the stromal response to tumor invasion, and there is evidence that these cells may be a prognosticator of malignant potential. IL-1, TGF-beta, chemokines, and serum amyloid P modulate the appearance and function of fibrocytes. Fibrocytes themselves produce inflammatory cytokines, growth factors, and chemokines. The intercellular signals that modulate fibrocyte trafficking, proliferation, and differentiation are only partially defined, but a better understanding of these signals enable new therapies to prevent pathologic fibrosis or to improve the tissue repair response.

Animals↗
PubMed2006

Nephrogenic systemic fibrosis: an update.

Nephrogenic systemic fibrosis (NSF), previously known as nephrogenic fibrosing dermopathy, is an emerging systemic fibrosing disorder that develops in the setting of renal insufficiency. Since its recognition in 1997, several case reports of NSF have been published in the rheumatology literature, reflecting the increasing incidence and recognition of this disorder in the United States and abroad. As rheumatology professionals are commonly the first to encounter newly developing cases, it is imperative that they recognize the symptoms and comorbidities of NSF and initiate work-up and treatment. To date, the precise causes of NSF have not been established; however, several promising lines of inquiry have led to a new model of the disorder. This model speculates that circulating fibrocytes of bone marrow origin are aberrantly recruited to the skin and other systemic sites by a process likely triggered or exacerbated by endothelial damage.

Diagnosis, Differential↗
PubMed2006

The histopathology of primary cicatricial alopecia.

Alopecia typically is divided into cicatricial (scarring) and noncicatricial (nonscarring) forms. "Scarring" alopecia implies that follicular epithelium has been replaced by connective tissue and is therefore an irreversible process. In contrast, nonscarring alopecia is potentially reversible as follicular epithelia remain intact. Classification of cicatricial alopecia can be confusing and controversial as most disorders demonstrate overlapping clinical and histologic features. Herein, we present an overview of the histologic assessment of cicatricial alopecia, including an algorithmic approach to the evaluation of biopsy specimens from patients with scarring alopecia.

Alopecia↗
PubMed2006

Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy).

PURPOSE OF REVIEW: Nephrogenic systemic fibrosis, also known as nephrogenic fibrosing dermopathy, was first documented in 1997 as a scleroderma-like fibrosing entity of the skin in association with renal insufficiency. Rheumatologists, along with other specialists, may be the first to encounter these patients; and both a familiarity with the disorder and vigilance for its cardinal features is in order. This review provides an update and highlights recent theories, achievements and ongoing research in understanding this emerging and enigmatic disorder. RECENT FINDINGS: Clinical reports support the evidence of nephrogenic systemic fibrosis as a systemic disease and emphasize an increase in its recognition in the United States, Europe and Asia. The most recent work supports a model whereby circulating fibrocytes together with fibrogenic factors lead to the evolution of this disabling and sometimes fatal disorder. SUMMARY: While a specific cause of nephrogenic systemic fibrosis remains to be established, the pathogenesis seems to be multifactorial, with the postulated involvement of the circulating fibrocytes. Recent published data including information from the Yale University NSF Registry has shed light on the clinical spectrum, cause, pathogenesis and treatment options. Clinical awareness of nephrogenic systemic fibrosis is still emerging and future studies are warranted to clarify its etiopathogenesis and effective therapies.

Fibrosis↗
PubMed2005

Cellular digital fibromas: distinctive CD34-positive lesions that may mimic dermatofibrosarcoma protuberans.

BACKGROUND: Digital fibromas are common benign acral tumors typically reported as angiofibromas (AFs) or acquired digital fibrokeratomas (ADFs). Cellular variants are not well recognized. METHODS: We collected 14 acral fibrocytic lesions showing a spindle cell morphology from our files, and evaluated CD34, Factor XIIIa, epithelial membrane antigen (EMA), and S100 protein staining of these lesions. We compared the histologic and immunohistochemical features of these cellular fibromas with five digital AFs, five ADFs, and five digital dermatofibromas. RESULTS: The 14 cellular digital fibromas showed intersecting fascicles of thin delicate bland spindle cells in the superficial reticular dermis with a fibrotic-to-slight myxoid stroma. The spindle cells in all cases stained strongly for CD34, and only scattered stromal cells stained for Factor XIIIa. Five tested cases were negative for EMA and S100 protein. The digital AFs, fibrokeratomas, and dermatofibromas stained predominately for Factor XIIIa, with no or minimal staining for CD34. CONCLUSIONS: These findings suggest that a subset of digital fibromas is characterized by a dense cellular proliferation of CD34-positive spindle cells. Awareness of this variant of digital fibroma and its staining pattern is critical in preventing misdiagnosis as dermatofibrosarcoma protuberans, particularly in superficial biopsies.

Adult↗
PubMed2005

CD56 staining in Merkel cell carcinoma and natural killer-cell lymphoma: magic bullet, diagnostic pitfall, or both?

BACKGROUND: Antibodies to CD56 label natural killer (NK) cell lymphomas and neuroendocrine tumors such as Merkel cell carcinoma (MCC). In MCC altered by crush artifact or obscured by lymphocytes, the histologic features coupled with CD56 positivity can lead to an erroneous impression of NK-cell lymphoma. METHODS: Eighteen cases of MCC were stained for CD56, CK20, MNF116, and pankeratin. The results were compared to histologic features and CD56 staining pattern of three NK-cell lymphomas. RESULTS: Three of 18 cases of MCC histologically resembled lymphoma, and CD56 positivity with CD3 and CD20 negativity initially raised the possibility of NK-cell lymphoma. Two additional cases were obscured by dense inflammation, again suggesting the diagnosis of lymphoma. Seventeen of 18 MCC labeled for CD56 and an equal number stained for CK20. All MCC tested were positive for CAM5.2 (14/14) and MNF116 (17/17). Antibodies to pankeratin labeled only one of 18 MCC. Staining for CD56 was stronger in MCC than NK-cell lymphomas. CONCLUSIONS: CD56 is a sensitive marker for MCC as well as for NK-cell lymphoma, but is not specific. Importantly, CD56 positivity in crushed or inflamed biopsies of MCC may lead to an erroneous impression of NK lymphoma. Awareness of this potential pitfall will prevent misdiagnosis. McNiff JM, Cowper SE, Lazova R, Subtil A, Glusac EJ. CD56 staining in Merkel cell carcinoma and natural killer-cell lymphoma: Magic bullet, diagnostic pitfall, or both?

Aged↗
PubMed2003

Nephrogenic fibrosing dermopathy: the first 6 years.

PURPOSE OF REVIEW: Nephrogenic fibrosing dermopathy (NFD) is a newly recognized scleroderma-like fibrosing skin condition. It develops in patients with renal insufficiency. This review summarizes recent case reports and examines theories of disease pathogenesis. Information from the Yale University NFD Registry Project, as well as published case reports, is included to provide a contextual framework upon which to base these theories. RECENT FINDINGS: Recent studies have contributed to a clearer definition of the clinical spectrum, epidemiology, and pathogenesis of NFD. The findings of yellow scleral plaques and circulating antiphospholipid antibodies have been proposed as markers of NFD in recent case reports. In addition, epidemiologic data have yielded several distinct clinical patterns of disease onset. Lastly, dual immunohistochemical staining for CD34 and procollagen in the spindle cells of NFD suggest that the dermal cells of NFD may represent circulating fibrocytes recruited to the dermis-a finding previously undescribed in normal skin. SUMMARY: Scenario classification of NFD is a means for simplifying the search for multifactorial disease triggers, and may be helpful in predicting prognosis and response to therapy. The technique of dual immunolabeling, although not yet fully characterized as a diagnostic test, may provide a sensitive and specific method of diagnosis, as well as a starting point in the investigation of other cutaneous fibrosing disorders. The postulate that NFD may represent a systemic disorder mediated by aberrantly functioning circulating fibroblast precursor fibrocytes is explored.

Adolescent↗
PubMed2002

An investigation of apoptosis in androgenetic alopecia.

While the androgens, including dihydrotestosterone (DHT), have been implicated in the development of androgenetic alopecia (AGA), the exact mechanism by which they exert their effects is unknown. As apoptosis is an integral component of the normal cycling of human hair, we investigated individuals clinically affected by AGA to assess whether objective differences in the expression of apoptosis related immunohistochemical markers could be observed in scalp biopsies. Specimens from 13 alopecic male cadavers were stained with bcl-2 and terminal deoxynucleotidetransferase dUTP fluorescein nick end-labeling (TUNEL) methods to assess apoptotic activity in affected and unaffected areas of the scalp. Immunoreactivity was analyzed by quantifying nuclear staining differences within the same individual. Sections from two living human volunteers were obtained to establish the method validity. Significant differences in bcl-2 expression were observed between areas of the scalp clinically affected and unaffected by AGA. The Gaussian distribution of bcl-2 staining suggests that a relatively uniform population of follicles exists at the frontal hairline and/or synchrony of follicular cycling occurs in AGA. The apoptosis "hot spot" described by TUNEL staining in the bulge-isthmus region of the murine follicle is also identifiable in the human follicle.

Aged↗
PubMedDate not supplied

Nephrogenic systemic fibrosis: an emerging threat among renal patients.

Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy, is a scleroderma-like disease of the skin observed in patients with renal insufficiency. Since its recognition in 1997, relatively little has been published in the nephrology literature, despite indications that the disorder is becoming increasingly recognized in the United States and abroad. As nephrology professionals may be the first to encounter newly developing cases of NSF, it becomes imperative that they be able to recognize the symptoms and comorbidities and initiate tests and treatment. To date, the cause of NSF has not been established. Recent observations indicate that specific cells normally involved in wound repair and tissue remodeling may be aberrantly recruited to the skin and soft tissues of NSF patients.

Comorbidity↗