Inhibition of trypanothione reductase by substrate analogues.

Trypanothione reductase (TR) catalyzes the NAPDH-dependent reduction of the spermidine-glutathione conjugate trypanothione, an antioxidant found in Trypanosomatid parasites. TR plays an essential role in the parasite's defense against oxidative stress and has emerged as a prime target for drug development. Here we report the synthesis of several trypanothione analogues and their inhibitory effects on T. cruzi TR. All are competitive inhibitors with K(i) values ranging from 30 to 91 microM.

Fine-needle aspiration biopsy of gouty tophi: lessons in cost-effective patient management.

Gout, a disease resulting from the effects of hyperuricemia and a crystal-induced arthropathy, may produce soft tissue masses (tophi) which mimick neoplasia clinically and radiographically. We have recently diagnosed three cases of gouty tophus, two of which were clinically suspected to represent sarcomas, by fine-needle aspiration biopsy (FNAB) after extensive radiologic and clinical evaluation. There were two women and one man. aged 71, 73, and 50 yr, with palpable soft tissue masses that involved the right forearm, right hand, and right foot, respectively, Biopsies were obtained by using 25-gauge needles without the aid of general anesthesia. Morphologically, aggregates and disassociated slender, needle-shaped crystals were abundant and easily recognized on both Diff-Quik and Papanicolaou stains. By using a polarizing microscope with a first-order red compensator, the crystals showed negative birefringence, characteristic of sodium urate. Benign-appearing histiocytes, foreign-body-type giant cells, neutrophils, and amorphous debris were scattered among the diagnostic crystals. The diagnosis of gouty tophus can be easily established with FNAB in conjunction with compensated polarizing microscopy. Application of FNAB in the initial evaluation of appropriate soft-tissue masses provides a cost-effective diagnostic method, preventing more costly and often unnecessary clinical and radiologic tests.

Dedifferentiated chondrosarcoma in patients with multiple osteochondromatosis: report of a case and review of the literature.

Multiple osteochondromatosis (MOS) is a familial disorder of autosomal dominant transmission characterized by the development of multiple exostoses and often derangements of epiphyseal cartilage, sometimes resulting in long bone growth retardation. Patients with the disorder appear to be at increased risk for developing secondary chondrosarcomas. Rarely, dedifferentiated chondrosarcomas may also occur. We report a single case of a 27-year-old man with multiple osteochondromatosis who developed a fatal dedifferentiated chondrosarcoma. Radiographically, the neoplasm arose from the pelvis completely destroying the left pubic ramus. Subsequently, the patient underwent preoperative chemotherapy followed by a left external hemipelvectomy. On pathologic examination, the tumor was characterized by high-grade pleomorphic sarcoma sharply juxtaposed to a low-grade chondrosarcoma. The patient ultimately died of widespread metastatic sarcoma.

Chondroblastoma of bone: use of fine-needle aspiration biopsy and potential diagnostic pitfalls.

Chondroblastoma of bone is a well-characterized entity. When the radiographic features are classic and the lesion is present in typical locations (i.e., epiphysis of a long bone), the diagnosis is often easily established by fine-needle aspiration biopsy and/or surgical curettage. Tumors in unusual locations, in older patients, or when complicated by aneurysmal bone cysts may pose more diagnostic difficulty. We report four examples (three primary and one-recurrent) of chondroblastoma of bone diagnosed by fine-needle aspiration biopsy. All patients were men, ranging from 18 to 28 yr of age. Sites of involvement included the acromion process of the scapula, left humerus, right ischium, and left distal femur. Three of the tumors were diagnosed as chondroblastoma on fine-needle aspiration cytology; the fourth case, involving the scapula, consisted mostly of a large aneurysmal bone cyst and remained unrecognized until surgical curettage was performed. Typical-appearing chondroblasts were present in three of the cases; osteoclast-type giant cells were observed in all four cases. Matrix material consistent with chondroid was also identified in all cases. We believe that in the absence of inflammatory cells, the presence of classic-appearing chondroblasts, even without chondroid matrix, is sufficient for a diagnosis of chondroblastoma of bone.

The spreadsheet and physician productivity.

Friction between medical education faculty members and other physicians at St. Vincent Medical Center, Toledo, Ohio, led to a program to assess both the costs and the contribution of the teaching faculty to the overall goals of the institution. Because the existing information system proved to be unequal to the task, a specially designed spreadsheet system was developed to be used for medical education physicians. The computer-based system that was developed permits a detailed analysis of the productivity of these physicians. More important, it allowed the medical education function to provide solid justification of its efforts on behalf of the medical center.