Clinical problem-solving. A fractured diagnosis.
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Accidental Falls↗
Biomedical subjects
Tali Cukierman
Publications and source records attributed to Tali Cukierman.
Anterior uveitis as a complication of treatment with high dose cytosine-arabinoside.
We present a case of a 21-year-old woman suffering from diffuse large B-cell lymphoma who developed acute anterior uveitis shortly after completing chemotherapeutic course with HYPER-CVAD protocol (cyclophosphamide, doxorubicin, vincristine, and dexamethasone) alternating with methotrexate and high-dose cytosine-arabinoside (HIDAC), with poor adherence to recommended prophylactic treatment with saline eye drops. Complete resolution of her symptoms was achieved within a few days of treatment with topical steroids. To our knowledge this is the first report of acute anterior uveitis secondary to treatment with HIDAC. Differential diagnosis and a suggested mechanism are discussed.
Adult↗
Basic residues in azurocidin/HBP contribute to both heparin binding and antimicrobial activity.
Azurocidin/CAP37/HBP is an antimicrobial and chemotactic protein that is part of the innate defenses of human neutrophils. In addition, azurocidin is an inactive serine protease homolog with binding sites for diverse ligands including heparin and the bovine pancreatic trypsin inhibitor (BPTI). The structure of the protein reveals a highly cationic domain concentrated on one side of the molecule and responsible for its strong polarity. To investigate the role of this highly basic region, we produced three recombinant azurocidin mutant proteins that were altered in either one or both of two clusters of 4 basic residues located symmetrically on each side of a central cleft in the cationic domain. Two of the mutant proteins (Loop 3: R5Q, K6Q, R8Q, and R10Q; Loop 4: R61Q, R62Q, R63Q, and R65Q) exhibited little or no change in heparin and BPTI binding or in antimicrobial function. In contrast, the Loop 3/Loop 4 mutant (R5Q, K6Q, R8Q, R10Q, R61Q, R62Q, R63Q, and R65Q) in which all 8 basic residues were replaced showed greatly decreased ability to bind heparin and to kill Escherichia coli and Candida albicans. Thus, we report that the 8 basic residues that were altered in the Loop 3/Loop 4 mutant contribute to the ability of the wild-type azurocidin molecule to bind heparin and to kill E. coli and C. albicans. Because BPTI binding was comparable in wild-type and Loop 3/Loop 4 mutant protein, we conclude that the same 8 basic residues are not involved in the binding of BPTI to azurocidin, supporting the notion that the binding site for BPTI is distinct from the site involved in heparin binding and antimicrobial activity. Finally, we show that removal of all 4 positively charged amino acids in the 20-44 azurocidin sequence (DMC1: R23Q,H24S,H32S,R34Q), a region previously thought to contain an antimicrobial domain, does not affect the activity of the protein against E. coli, Streptococcus faecalis, and C. albicans.
Amino Acid Sequence↗
Chronic lymphocytic leukemia presenting with extreme hyperleukocytosis and thrombosis of the common femoral vein.
Very few case reports dealing with chronic lymphocytic leukemia (CLL) and hyperleukocytosis have been reported in the medical literature and none with venous thrombosis as a complication. Here, we describe a 73-year-old woman who presented with newly diagnosed CLL, leukostasis, and hyperleukocytosis (2000 x 10(9)/l), affecting the respiratory and nervous system. In addition, she also had deep vein thrombosis (DVT). Although hypercoagulability and thrombosis are well-described phenomena in solid tumors and in myeloproliferative neoplasms, CLL is generally not associated with an acquired coagulopathy. We hypothesize that in our patient the extreme number of circulating lymphocytes resulted in an abnormal accumulation of lymphocytes possibly causing stasis and occlusion of a larger vessel, which resolved after leukopheresis. The patient has since been successfully maintained with chemotherapy. We conclude that leukopheresis should be considered as the therapy of choice in CLL patients presenting with major complications of leukostasis.
Aged↗