Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment.

High fevers and/or rashes prior to neutrophil engraftment are frequently observed after umbilical cord blood (UCB) transplantation, and the condition is referred to as pre-engraftment syndrome (PES). Few studies have evaluated the risk factors for and treatment response to PES. Therefore, we retrospectively characterized PES in 57 consecutive engrafted patients (≥ 12 years old) who received myeloablative dual UCB transplantation. All patients received TBI (≥ 13.2 Gy)-based myeloablative conditioning. Tacrolimus (n=35) or CYA (n=22) combined with mycophenolate mofetil was used as GVHD prophylaxis. PES was defined as the presence of non-infectious fever (≥ 38.5 °C) and/or rash prior to or on the day of neutrophil engraftment. The incidence (95% confidence interval) of PES was 77% (66-88%). The incidence of PES was significantly higher in patients who received CYA as a GVHD prophylaxis than those who received tacrolimus (P<0.001), and this association was confirmed in the multivariate analysis. The occurrence of PES did not impact OS or tumor relapse, although it may have increased non-relapse mortality (P=0.071). The incidence of acute GHVD or treatment-related mortality was not influenced by the choice to use corticosteroids to treat PES. This study suggests that use of CYA for GVHD prophylaxis increases the risk of PES following dual UCB transplantation.

Clear cell sarcoma of the kidney: an unusual presentation and review of the literature.

PURPOSE: To describe a child with clear cell sarcoma of the kidney (CCSK) with an unusual presentation, including a primary tumor of the left kidney with metastases to the right kidney and soft tissues of the lower extremities, and to review the literature. PATIENT AND METHODS: An 8-month-old infant presented with hypertension, an abdominal mass, and soft tissue masses in the left thigh and right foot. Imaging studies revealed a large left-sided renal tumor, left paravertebral soft tissue masses, and left thigh mass. At laparotomy, a lesion was noted in the lower pole of the contralateral kidney. CCSK with metastases to the contralateral kidney and to the soft tissues of left thigh, right foot, and left paravertebral region was diagnosed on histopathologic examination. RESULTS: Multimodal oncologic treatment included surgery, chemotherapy, and radiotherapy. Three months after completion of therapy, a soft tissue lesion in the left arm and, later, soft tissue lesions involving multiple parts of the body developed. The patient died 18 months after diagnosis without clinical or radiographic evidence of bone involvement. CONCLUSIONS: In a review of the literature, CCSK is most commonly associated with bone and lung metastases. Soft tissue involvement is uncommon. Metastasis to the contralateral kidney at initial diagnosis has not previously been reported. This case represents an unusual metastatic pattern of CCSK.

Regulation of matrix metalloproteinases and plasminogen activator inhibitor-1 synthesis by plasminogen in cultured human vascular smooth muscle cells.

Plasmin and matrix metalloproteinases (MMPs) both participate in extracellular matrix remodeling. This study examined the effects of tumor necrosis factor-alpha (TNF-alpha) and plasminogen on collagenase, stromelysin, and plasminogen activator inhibitor-1 (PAI-1) synthesis of collagenase and stromelysin, which remained predominantly in proenzyme forms, as determined by Western analysis of culture media. In contrast, plasminogen and plasmin not only increased secretion of MMPs but also induced cleavage to their active forms. The serine protease inhibitor aprotinin inhibited this activation of MMPs by plasminogen and plasmin. TNF-alpha reduced plasminogen-induced activation of MMPs, suggesting induction of an inhibitor or plasmin generation, such as PAI-1. Enzyme-linked immunosorbent assay of culture media showed that TNF-alpha (10 ng/mL) increased PAI-1 secretion by 4.2 fold compared with control (105.5 +/- 9.6) versus 24.9 +/- 1.7 ng/mL, n = 3). Surprisingly plasminogen also increased PAI-1 secretion by vascular SMCs (3.6-fold over control). These results demonstrate coordination of cytokines and serine proteases in regulating MMP secretion and activation. In addition, the induction of PAI-1 by TNF-alpha and plasminogen suggests a negative feedback mechanisms limit both plasmin-mediated and MMP-mediated matrix degradation.

Synthesis and pharmacological properties of some 4-amino-5-substituted thiazole-2(3H)-thiones and thiazolo(4,5-d)pyrimidin-7(6H)-one-2(3H)-thiones.

4-Amino-5-substituted thiazole-2(3H)-thiones and thiazolo(4,5-d)-pyrimidin-7(6H)-one-2(3H)-thiones have been synthesized and screened for antimicrobial and pharmacological activities. Significant analgesic, antiinflammatory, anticonvulsant and antimicrobial properties have been found in some of the compounds synthesized. Analgesic and antiinflammatory activities are reported for the first time in thiazole-2(3H)-thiones.

Synthesis of 3-substituted thieno [2, 3-d] pyrimidin-4(3H)-one-2-mercaptoacetic acids and their ethyl esters for pharmacological screening.

3-Substituted thieno [2, 3-d] pyrimidin-4(3H)-one-2-mercaptoacetic acids and their ethyl esters were synthesized from 2-mercaptothieno [2, 3-d] pyrimidin-4(3H]-ones, which were obtained by cyclization of thienylthioureas in acidic medium. Analgesic, anti-inflammatory, and anticonvulsant activities were found in some of these compounds. Significant antimicrobial activity was exhibited by thienylthioureas.